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An asymmetric formal synthesis of (+)‐phomactin A has been accomplished. The key steps in the synthetic strategy included establishing the AB ring system in one‐pot via Prins/Conia‐ene cascade cyclization reaction and the C ring formation via γ‐hydroxylation of enone in the late‐stage of the synthesis. The two major fragments are readily prepared from (+)‐pulegone and geraniol via a modified Eschenmoser–Tanabe fragmentation strategy in 6 steps and a Sharpless asymmetric epoxidation/hydrozirconation/ Roskamp reaction sequence in 11 steps respectively. [ABSTRACT FROM AUTHOR]

Abstraction-based techniques are an attractive approach for synthesizing correct-by-construction controllers to satisfy high-level temporal requirements. A main bottleneck for successful application of these techniques is the memory requirement, both during controller synthesis (to store the abstract transition relation) and in controller deployment (to store the control map). We propose memory-efficient methods for mitigating the high memory demands of the abstraction-based techniques using neural network representations. To perform synthesis for reach-avoid specifications, we propose an on-the-fly algorithm that relies on compressed neural network representations of the forward and backward dynamics of the system. In contrast to usual applications of neural representations, our technique maintains soundness of the end-to-end process. To ensure this, we correct the output of the trained neural network such that the corrected output representations are sound with respect to the finite abstraction. For deployment, we provide a novel training algorithm to find a neural network representation of the synthesized controller and experimentally show that the controller can be correctly represented as a combination of a neural network and a look-up table that requires a substantially smaller memory. We demonstrate experimentally that our approach significantly reduces the memory requirements of abstraction-based methods. We compare the performance of our approach with the standard abstractionbased synthesis on several models. For the selected benchmarks, our approach reduces the memory requirements respectively for the synthesis and deployment by a factor of 1.31x105 and 7.13x10³ on average, and up to 7.54 x 105 and 3.18 x 104. Although this reduction is at the cost of increased off-line computations to train the neural networks, all the steps of our approach are parallelizable and can be implemented on machines with higher number of processing units to reduce the required computational time. [ABSTRACT FROM AUTHOR]

We consider the problem of privacy enforcement for dynamic systems using the technique of obfuscation. Our approach captures the trade-off between privacy and utility, in a formal reactive framework. Specifically, we model a dynamic system as an automaton or labeled transition system with predefined secret behaviors. The system generates event strings for some useful computation (utility). At the same time, it must hide its secret behaviors from any outside observer of its behavior (privacy). We formally capture both privacy and utility specifications within the model of the system. We propose as obfuscation mechanism for privacy enforcement the use of edit functions that suitably alter the output behavior of the system by inserting, deleting, or replacing events in its output strings. The edit function must hide secret behaviors by making them observationally equivalent to non-secret behaviors, while at the same time satisfying the utility requirement on the output strings. We develop algorithmic procedures that synthesize a correct-by-construction edit function satisfying both privacy and utility specifications. The synthesis procedure is based on the solution of a game where the edit function must react to the system moves by suitable output editing. After presenting an explicit algorithm for solving for the winning strategies of the game, we present two complementary symbolic implementations to address scalability of our methodology. The first symbolic implementation uses a direct encoding of the explicit algorithm using binary decision diagrams (BDDs). The second symbolic implementation reframes the synthesis of edit functions as a supervisory control problem and then applies a recently-developed tool for solving supervisory control problems using BDDs. Experimental results comparing the two symbolic implementations are provided.

Aurantioclavine, isolated by Kozlovskii from Penicillium aurantiovirens, is a unique member of the 3,4‐disubstituted indole alkaloids distinguished by an azepino[5,4,3‐cd]indole. As an essential intermediate in the biosynthesis of the complex polycyclic alkaloids of the fungal communesin, it has attracted considerable attention as a synthetic target. The development of various synthetic strategies for their application in total synthesis has been described. An overview focused on the synthesis of aurantioclavine from its first synthesis to the most recent one is present. [ABSTRACT FROM AUTHOR]

Formal syntheses of teadenols A and B are achieved via a key Pd-catalyzed 6- endo cyclization of a phenol possessing a vinyl -epoxide moiety. Although 5- exo and 6- endo cyclizations compete during cyclizations of epoxides with a nucleophilic moiety at the 5-position, 6- endo cyclization is realized by using a palladium catalyst. [ABSTRACT FROM AUTHOR]

The focus review discusses the synthesis of an important member of the monoterpene indole alkaloid family, mersicarpine. Biosynthetically, mersicarpine, isolated from the Kopsia fruticosa and Kopsia arborea, is proposed to share the same biogenetic pathway as melodinine E and leuconolam, and has a fused tetracyclic [6.5.6.7] ring system characterized by an unusual tetrahydro‐2H‐azepine ring and a hemiaminal motif. As a consequence, this intriguing structural feature has attracted considerable attention from synthetic chemists. The review focuses on the synthesis of mersicarpine from its first synthesis to the most recent one, ranging from 2008–2022. [ABSTRACT FROM AUTHOR]

STRATEGIES FOR THE SYNTHESIS OF LYSERGIC ACID. (+)-Lysergic acid [(+)-1] is a precursor of several substances with well-established pharmacological properties, including some drugs approved and commercialized around the world. Thus, the importance of (+)-1 as a synthetic target becomes undoubted and various strategies for the synthesis of its tetracyclic core have been reported in the literature. Therefore, in this review article we will address in chronological order the total and formal syntheses of lysergic acid (1), separating them into racemic and chiral/asymmetric syntheses. Until now, there are 24 syntheses described in the literature, namely, 11 total and 13 formal syntheses. Considering all the syntheses accomplished, 15 were planned to produce (±)-lysergic acid [(±)-1] and 9 presented routes to eventually provide (+)-lysergic acid [(+)-1]. A significant evolution regarding approaches and efficiency may be observed since the first synthesis of (±)-1 until the last asymmetric synthesis of (+)-1.

We introduce a framework for the control of discrete-time switched stochastic systems with uncertain distributions. In particular, we consider stochastic dynamics with additive noise whose distribution lies in an ambiguity set of distributions that are ɛ − close, in the Wasserstein distance sense, to a nominal one. We propose algorithms for the efficient synthesis of distributionally robust control strategies that maximize the satisfaction probability of reach-avoid specifications with either a given or an arbitrary (not specified) time horizon, i.e., unbounded-time reachability. The framework consists of two main steps: finite abstraction and control synthesis. First, we construct a finite abstraction of the switched stochastic system as a robust Markov decision process (robust MDP) that encompasses both the stochasticity of the system and the uncertainty in the noise distribution. Then, we synthesize a strategy that is robust to the distributional uncertainty on the resulting robust MDP. We employ techniques from optimal transport and stochastic programming to reduce the strategy synthesis problem to a set of linear programs, and propose a tailored and efficient algorithm to solve them. The resulting strategies are correctly refined into switching strategies for the original stochastic system. We illustrate the efficacy of our framework on various case studies comprising both linear and non-linear switched stochastic systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • Stereoselective access to thienamycin from readily available starting materials. • Practical access to the core of frontline antibiotics. • Asymmetric reduction of carbonyls leveraging robust and economical reagents. Thienamycin is a carbapenem antibiotic with potent activity against gram-negative and gram-positive bacteria. Due to its promising activity but lack of chemical stability, thienamycin serves as inspiration for new synthetic antibiotic scaffolds. In this study, we report a nine-step enantioselective formal synthesis of thienamycin. Our route utilizes an asymmetric reduction, enabled by NaBH 4 and d -tartaric acid, followed by a series of diastereoselective reactions to access the key azetidinone precursor to thienamycin. This azetidinone precursor could be used as an intermediate to further develop and expand the scope of next-generation beta-lactam antibiotic scaffolds. [ABSTRACT FROM AUTHOR]

Aplykurodinone‐1, a marine steroid with intriguing molecular architecture and promising biological activities, has captured the attention of many synthetic chemists. In this paper we have overviewed the synthetic approaches of aplykurodinone‐1 to date, with a focus on the novel strategies utilized to improve the synthetic efficiency. This review summarizes the contribution of different research groups in the total or formal synthesis of aplykurodinone‐1 in either racemic or enantiomeric form. [ABSTRACT FROM AUTHOR]

A stereoselective formal synthesis of platencin was accomplished from bromophenol 8 in eleven synthetic steps with 6 % overall yield. The intramolecular Diels‐Alder reaction of masked o‐benzoquinone, intramolecular aldol condensation, and stereoselective hydrogenation were the key steps in the construction of the tricyclic core of platencin. [ABSTRACT FROM AUTHOR]

An asymmetric formal synthesis of trichodermamides B and C was achieved in 15 steps based on a tyrosine ester chiral-pool approach. Key features of this synthesis include stereoselective construction of a cis -1,2-oxazadecaline core by an acid-mediated tandem deprotection–intramolecular oxy-Michael reaction, oxime ether formation via an N -bromination–elimination sequence, and diene construction by a palladium-catalyzed demonomethylcarbonation. [ABSTRACT FROM AUTHOR]

This paper describes current work on framing the model predictive control (MPC) of cyber-physical systems as synthesis from signal temporal logic (STL) specifications. We provide a case study using a simplified power grid model with uncertain demand and generation; the model-predictive control problem here is that of the ancillary service power flow from the buildings. We show how various relevant constraints can be captured using STL formulas, and incorporated into an MPC framework. We also provide preliminary simulation results to illustrate the promise of the proposed approach.

In this paper, we propose a compositional framework for the construction of discrete-time finite abstractions, also known as finite Markov decision processes, from continuous-time stochastic hybrid systems by quantifying the distance between their outputs in a probabilistic setting. The proposed scheme is based on the notion of stochastic simulation functions , which is used to relate continuous-time stochastic systems with their discrete-time counterparts. Accordingly, one can employ discrete-time abstract systems as substitutions of the continuous-time ones in the controller design process with guaranteed error bounds on their output trajectories. To this end, we first derive sufficient small-gain type conditions for the compositional quantification of the probabilistic distance between the interconnection of original continuous-time stochastic hybrid systems and their discrete-time (finite or infinite) abstractions. We then construct finite abstractions together with their corresponding stochastic simulation functions for a particular class of nonlinear stochastic hybrid systems having some stability property. We illustrate the effectiveness of the proposed results by applying our approaches to the temperature regulation in a circular building and constructing compositionally a discrete-time abstraction from its original continuous-time dynamics in a network containing 1000 rooms. We employ the constructed discrete-time abstractions as substitutes to compositionally synthesize policies regulating the temperature of each room for a bounded time horizon. [ABSTRACT FROM AUTHOR]

A concise formal synthesis of (±)-aplykurodinone-1 starting from a commercially available material and based on the indium-catalyzed Conia-ene reaction has been accomplished. The synthesis features a Riley selenium dioxide oxidation, a Krapcho dealkoxycarbonylation, and a ring-closing metathesis approach. The synthetic strategy was also supported by a Saegusa oxidation and a classic Michael 1,4-conjugate addition. [ABSTRACT FROM AUTHOR]

In this work, we study verification and synthesis problems for safety specifications over unknown discrete-time stochastic systems. When a model of the system is available, barrier certificates have been successfully applied for ensuring the satisfaction of safety specifications. In this work, we formulate the computation of barrier certificates as a robust convex program (RCP). Solving the acquired RCP is hard in general because the model of the system that appears in one of the constraints of the RCP is unknown. We propose a data-driven approach that replaces the uncountable number of constraints in the RCP with a finite number of constraints by taking finitely many random samples from the trajectories of the system. We thus replace the original RCP with a scenario convex program (SCP) and show how to relate their optimizers. We guarantee that the solution of the SCP is a solution of the RCP with a priori guaranteed confidence when the number of samples is larger than a specific value. This provides a lower bound on the safety probability of the original unknown system together with a controller in the case of synthesis. We also discuss an extension of our verification approach to a case where the associated robust program is non-convex and show how a similar methodology can be applied. Finally, the applicability of our proposed approach is illustrated through three case studies. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a compositional scheme for the construction of finite abstractions (a.k.a. symbolic models) of interconnected discrete-time control systems. The compositional scheme is based on small-gain type reasoning. In particular, we use a notion of so-called alternating simulation functions as a relation between each subsystem and its symbolic model. Assuming some small-gain type conditions, we construct compositionally an overall alternating simulation function as a relation between an interconnection of symbolic models and that of original control subsystems. In such compositionality reasoning, the gains associated with the alternating simulation functions of the subsystems satisfy a certain "small-gain" condition. In addition, we introduce a technique to construct symbolic models together with their corresponding alternating simulation functions for discrete-time control subsystems under some stability property. Finally, we apply our results to the temperature regulation in a circular building by constructing compositionally a finite abstraction of a network containing N rooms for any N ≥ 3. We use the constructed symbolic models as substitutes to synthesize controllers compositionally maintaining room temperatures in a comfort zone. We choose N = 1000 for the sake of illustrating the results. We also apply our proposed techniques to a nonlinear example of a fully connected network in which the compositionality condition still holds for any number of components. In these case studies, we show the effectiveness of the proposed results in comparison with the existing compositionality technique in the literature using a dissipativity-type reasoning. [ABSTRACT FROM AUTHOR]

This paper is concerned with a compositional approach for constructing infinite abstractions of interconnected discrete-time stochastic control systems. The proposed approach uses the interconnection matrix and joint dissipativity-type properties of subsystems and their abstractions described by new notions of so-called stochastic storage functions. The interconnected abstraction framework is based on new notions of so-called stochastic simulation functions, constructed compositionally using stochastic storage functions of components. Using stochastic simulation functions, one can quantify the distance between original interconnected stochastic systems and interconnected abstractions in the probabilistic setting. Accordingly, one can leverage the proposed results to perform analysis and synthesis over abstract interconnected systems, and then carry the results back over concrete ones. In the first part of the paper, we derive dissipativity-type compositional reasoning for the quantification of the distance in probability between the interconnection of stochastic control subsystems and that of their abstractions. Moreover, we focus on a class of discrete-time nonlinear stochastic control systems with independent noises in the abstract and concrete subsystems, and propose a computational scheme to construct abstractions together with their corresponding stochastic storage functions. In the second part of the paper, we consider specifications expressed as syntactically co-safe linear temporal logic formulae and show how a synthesized policy for the abstract system can be refined to a policy for the original system while providing a guarantee on the probability of satisfaction. We demonstrate the effectiveness of the proposed results by constructing an abstraction (totally 3 dimensions) of the interconnection of three discrete-time nonlinear stochastic control subsystems (together 222 dimensions) in a compositional fashion such that the compositionality condition does not require any constraint on the number or gains of the subsystems. We also employ the constructed abstraction as a substitute to synthesize a controller enforcing a syntactically co-safe linear temporal logic specification. [ABSTRACT FROM AUTHOR]

A concise enantioselective synthesis of A/B bicyclic segment of naturally occurring α-pyrone meroterpenoid pyripyropene A is achieved in 9 steps (LLS) and 7.5% yield starting from R -(−)-carvone. The significant points of the synthesis include: (1) an intramolecular 1, 3-dipolar cycloaddition reaction to construct the A ring and assemble C4 quaternary carbon stereocenter as well; (2) reductive cleavage of the oxazole motif utilized Raney Ni/B(OCH 3) 3. Image 1 [ABSTRACT FROM AUTHOR]

We describe a new and straightforward approach to the formal synthesis of the hepatitis B virus inhibitor entecavir, an important hepatitis B drug, in ten steps overall. Key features of the route are a Morita–Baylis–Hillman reaction, a Sharpless asymmetric epoxidation, a reductive epoxide opening of an α,β-epoxy ketone, and a Riley selenium dioxide oxidation. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Formal synthesis of (±)-aplykurodinone-1 was achieved in 6 steps. • An intramolecular Michael addition was employed as the key to generate ring B. • Key intermediates and final product were determined by single-crystal X-ray. Abstract A concise and straightforward formal synthesis of (±)-aplykurodinone-1, a degraded steroid natural product isolated from sea hare Syphonota geographica is described, based on an intramolecular Michael addition. The route also includes an intermolecular Michael addition, a Riley selenium dioxide oxidation, and a Krapcho dealkoxycarbonylation. The relative stereochemistries of key intermediates have been determined through single-crystal X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Abstract A short, simple and convenient chiron approach to (3 R ,4 S ,5 R)-(−)-3,5-dihydroxy-4-decanolide, a hitherto unknown diastereomer of the reported structure of a naturally occurring acetogenin, (+)-polyporolide has been accomplished starting from a commercially available, inexpensive chiral pool molecule D-(+)-mannitol in nine efficient steps. An advanced intermediate synthesized from D-(+)-mannitol in six steps toward this end was further employed successfully to access two different natural products bearing two contiguous stereogenic centers. As a result, first chiron approach to formal total synthesis of an amide alkaloid, (4 R ,5 R ,2 E)-4,5-dihydroxy-1-(piperidin-1-yl)dec-2-en-1-one and total synthesis of a male sex pheromone in parasitic Hymenoptera, (4 R ,5 R)-(−)-5-hydroxy-4-decanolide have also been achieved. Graphical abstract Image 1 Highlights • Chiron approach ensured absolute stereochemistry of all the compounds synthesized. • Three different optically pure target molecules were synthesized via a carbohydrate derived chiral template. • A diastereomer of the proposed structure of (+)-polyporolide was prepared for the first time. • Chiron approach was utilized for the first time to access an amide alkaloid from Piper nigrum. [ABSTRACT FROM AUTHOR]

Mankind has been searching for anticancer drugs from nature and artificial compounds. Since the discovery of englerin A, a guaiane sesquiterpene possessing the characteristic tricyclic 5–6‐5 fused ring framework with contiguous seven stereogenic centers and isolated from Phyllanthus engleri, many synthetic groups have enthusiastically launched and accomplished its the chemical synthesis. All the synthetic groups focused on how to efficiently construct the tricyclic framework containing oxygen bridge with various approaches. In this review, the total and formal syntheses of englerin A reported to date are summarized. Terpenoids: Since the discovery of englerin A, a guaiane sesquiterpene possessing the characteristic tricyclic 5‐6‐5 fused ring framework with contiguous seven stereogenic centers, many synthetic groups have accomplished its chemical synthesis. This Focus Review covers various approaches towards the total syntheses of englerin A. [ABSTRACT FROM AUTHOR]

A short enantioselective formal synthesis of the antibiotic natural product platencin is reported. Key steps in the synthesis include enantioselective decarboxylation alkylation, aldehyde/olefin radical cyclization, and regioselective aldol cyclization. [ABSTRACT FROM AUTHOR]

A stereocontrolled formal synthesis of platencin was accomplished in 11 steps from a bromophenol derivative, with an overall yield of 13 %. The intermolecular Diels–Alder reaction of masked o‐benzoquinone and an aldol condensation were the key steps in the construction of the tricyclic core of platencin. [ABSTRACT FROM AUTHOR]

Highlights • A formal approach is presented to synthesize controller for Barcelona wastewater system. • We employ signal temporal logic to express the desired closed-loop behavior. • We use robust MPC strategy to incorporate the new measurements in the optimization. • The optimization is transformed to non-convex MIQP and solved iteratively. • The approach is applied to a catchment of Barcelona wastewater system with 12 tanks. Abstract We present an approach for formal controller synthesis of the Barcelona wastewater system. The goal of the controller is to minimize overflow in the system and to reduce environmental contamination (pollution). Due to the influence of sudden and unpredictable weather changes within the Mediterranean climate, we propose robust model predictive control strategy. This approach synthesizes control inputs (i.e., flows through network actuators) that make the system robust to uncertainties in the weather forecast; control inputs are updated in an online fashion to incorporate the newly available measurements from the system and the disturbances. We employ signal temporal logic as a formal mechanism to express the desired behavior of the system. The quantitative semantics of the logic is then used to encode the desired behavior in both the set of constraints and the objective function of the optimization problem. We propose a solution approach for the obtained worst-case optimization, which is based on transforming the nonlinear dynamics of the system into a mixed logical dynamical model. Then, we employ Monte Carlo sampling and dual reformulation to get a mixed integer linear or quadratic programming problem.The proposed approach is applied to a catchment of the Barcelona wastewater system to illustrate its effectiveness. [ABSTRACT FROM AUTHOR]

Abstract: Advanced intermediates for the syntheses of tetrodotoxin reported by the groups of Fukuyama, Alonso, and Sato were prepared. Key steps include the toluene dioxygenase mediated dihydroxylation of either iodobenzene or benzyl acetate. The resulting diene diols were transformed into Fukuyama's intermediate in six steps, into Alonso's intermediate in nine steps, and into Sato's intermediate in ten steps. [ABSTRACT FROM AUTHOR]

Abstract: Dibenzocyclooctadiene lignans are an interesting class of molecules because of their unique structure based on an axially chiral biaryl moiety as well as their significant biological activity. Herein, we describe the development of a palladium‐catalyzed atroposelective C−H alkynylation and its application in gram‐scale, stereocontrolled formal syntheses of (+)‐isoschizandrin and (+)‐steganone. tert‐Leucine was identified as an efficient, catalytic transient chiral auxiliary. A wide range of enantiomerically enriched biaryl compounds were prepared by this approach in good yields (up to 99 %) with excellent enantioselectivity (up to >99 % ee). [ABSTRACT FROM AUTHOR]

The direct catalytic asymmetric aldol reaction is an emerging catalytic methodology that provides atom-economical access to functionalized chiral building blocks. Thioamides are useful aldol donors due to their high-fidelity chemoselective enolization and divergent post-aldol transformations. Herein we describe the incorporation of an α-vinyl appendage on a thioamide, which expands the utility of aldol adducts for natural product synthesis. This vinylated thioamide was not accommodated under the previously identified catalyst settings, but the newly developed catalytic conditions furnished aldol products containing the pendant vinyl group. [ABSTRACT FROM AUTHOR]

Abstract: The direct catalytic asymmetric aldol reaction is an emerging catalytic methodology that provides atom‐economical access to functionalized chiral building blocks. Thioamides are useful aldol donors due to their high‐fidelity chemoselective enolization and divergent post‐aldol transformations. Herein we describe the incorporation of an α‐vinyl appendage on a thioamide, which expands the utility of aldol adducts for natural product synthesis. This vinylated thioamide was not accommodated under the previously identified catalyst settings, but the newly developed catalytic conditions furnished aldol products containing the pendant vinyl group. [ABSTRACT FROM AUTHOR]

[Display omitted] • Formal synthesis of isoquinocyclinone is described. • Key transformation is ortho- alkoxycarbonylmethylation of poly-substituted anthranol via diazoquinone. • Key intermediate lactone was constructed from 1,2-dihydrotetracene-1-carboxylic acid derivative via epoxidation. In this study, a formal synthesis of isoquinocyclinone is reported. Synthesis of key intermediate lactone 6 , an intermediate in Koert's s total synthesis of isoquinocyclinone, was succeeded. The lactone 6 was synthesized by using our developed diazo-transfer reaction of anthranol with 2-azido-1,3-dimethylimidazolinium chloride (ADMC) and alkoxycarbonylmethylation of diazoquinone as key reactions. [ABSTRACT FROM AUTHOR]