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C16H20N2O5, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 7.9179(7) Å, b = 10.1982(9) Å, c = 10.4144(8) Å, α = 76.184(7)°, β = 87.090 (7)°, γ = 73.500(8)°, V = 782.86(12) Å3, Z = 2, R gt(F) = 0.0458, wR ref(F 2) = 0.1333, T = 93 K.

β-Carboline bearing indole is one of the heterocyclic compounds that play a vital role in medicinal chemistry with various pharmacological effects such as anticancer, anti-acetylcholinesterase, anti-inflammation, antimalarial, antibacterial, anti-diabetic, and antioxidant. Over the last two decades, many studies on the synthesis and biological activity of indole β-carboline compounds have been conducted yet there is no appropriate data summary has been presented. Thus, the goal of this review was to highlight the synthesis pathway and bioactivity of substituted indole β-carboline reported from 2005 to date. In addition, this will encourage further investigation into the synthesis and evaluation of new indole β-carboline, in the hope of contributing to the development of potentially new medications for the treatment of various ailments. [ABSTRACT FROM AUTHOR]

C15H17N3O4, triclinic, P1̄ (no. 2), a = 10.5986(5) Å, b = 11.5298(5) Å, c = 13.5386(6) Å, α = 102.694(1)°, β = 102.999(1)°, γ = 108.918(1)°, V = 1446.03(11) Å3, Z = 4, Rgt(F) = 0.0525, wRref(F2) = 0.1526, T = 100(1) K.

C16H20N2O5, triclinic, P 1 ‾ (no. 2), a = 7.9179(7) Å, b = 10.1982(9) Å, c = 10.4144(8) Å, α = 76.184(7)°, β = 87.090 (7)°, γ = 73.500(8)°, V = 782.86(12) Å3, Z = 2, Rgt(F) = 0.0458, wRref(F2) = 0.1333, T = 93 K. [ABSTRACT FROM AUTHOR]

A series of novel potentially biologically active fused [5:7] oxazepanone γ-lactams were synthesized and described. A series of functional group transformations, namely amination, syn-hydrogenation and intramolecular annulation reactions were used to obtain the [5:7] oxazepanone γ-lactams in reasonable yields. In the diastereoselective fused-annulation for the formation of the secondary ring, steric constrain and cisgeometrical configuration of C-3 and C-4 substituents were observed as the predetermined factors. These ring annulations were purposely constructed to suit the physicochemical enhancement of the biological activity of the title compounds via SAR study of γ-lactams. [ABSTRACT FROM AUTHOR]

A multifaceted approach comprising MCR (multicomponent reaction), amination and stereoselective reduction reactions was used to synthesize new pyrrolidine-based iminosugars. The key step of this strategy involves the contruction of a highly functionalised pyrroldine ring skeleton through MCR approach. Subsequently, amination and reduction reactions to the ring skeleton provide a quick access to new pyrrolidine-based imino sugars. The iminosugars were then tested against alpha glucosidase activity in which one compound (4-((4-methoxyphenyl)amino)pyrrolidin-3-ol), was found to be the most potent at low dosage. [ABSTRACT FROM AUTHOR]

A new pathway for the synthesis of novel 3,4-fused pyrazolidinone γ-lactam (4) starting from 2,3-dioxo-4-carboxy-5-(substituted)pyrrolidines (1) was developed. The key synthetic strategy involved hydrazonation of the precursor 1 followed by subsequent reduction reaction of the enamino ester 2 and intramolecular cyclization reaction to furnish the unprecedented 3,4-fused pyrazolidinone γ-lactam (4) in reasonable yield. The structures were confirmed by spectroscopic methods and chemical transformation. [ABSTRACT FROM AUTHOR]

Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates. [ABSTRACT FROM AUTHOR]

C15H17N3O4, triclinic, P1̄ (no. 2), a = 10.5986(5) Å, b = 11.5298(5) Å, c = 13.5386(6) Å, α = 102.694(1)°, β = 102.999(1)°, γ = 108.918(1)°, V = 1446.03(11) Å3, Z = 4, Rgt(F) = 0.0525, wRref(F2) = 0.1526, T = 100(1) K. [ABSTRACT FROM AUTHOR]

C15H17N3O4, triclinic, P1̄ (no. 2), a = 10.5986(5) Å, b = 11.5298(5) Å, c = 13.5386(6) Å, α = 102.694(1)°, β = 102.999(1)°, γ = 108.918(1)°, V = 1446.03(11) Å3, Z = 4, Rgt(F) = 0.0525, wRref(F2) = 0.1526, T = 100(1) K. [ABSTRACT FROM AUTHOR]

28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel of S. aureus isolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58 S. aureus isolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50 values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for further in vivo investigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA. [ABSTRACT FROM AUTHOR]

C16H20N2O5, triclinic, P 1 ‾ (no. 2), a = 7.9179(7) Å, b = 10.1982(9) Å, c = 10.4144(8) Å, α = 76.184(7)°, β = 87.090 (7)°, γ = 73.500(8)°, V = 782.86(12) Å3, Z = 2, Rgt(F) = 0.0458, wRref(F2) = 0.1333, T = 93 K. [ABSTRACT FROM AUTHOR]

Introduction: Swainsonine, an α-mannosidase II inhibitor, demonstrated capability to inhibit glycosylation pathways during pre-clinical investigations. However, this compound fails in clinical trial due to severe side effects including pulmonary oedema and neurological disorders, primarily arise from simultaneous inhibition of both lysosomal α-mannosidase II and Golgi α-mannosidase. To address these challenges, swainsonine analogues exhibiting greater selectivity towards Golgi α-mannosidase, as oppose to lysosomal α-mannosidase, are needed. To create highly selective analogs, it is imperative to begin with the parent compound swainsonine prior substitution. As it is costly to purchase swainsonine directly, we tested and developing a synthesis scheme for the preparation of swainsonine using D-isoascorbic acid as the chiral starting material. Methods: The medicinal chemistry synthesis pathway for swainsonine involves a series of protection and deprotection steps. Key transformations in the process include Wittig olefination, Huisgen 1,3-dipolar cycloaddition and hydroboration-oxidation. Purification of the products was carried out using the classical column chromatography Si-gel G60 (230-400 mesh, Merck). The 1H and 13C NMR spectra was registered in CDCl3 with Joel Resonance ECZ400S 400 MHz (1H) and 100 MHz (13C), using TMS as the internal standard. High-resolution mass spectra (HRMS) were obtained on an Agilent 6520 Accurate-Mass Quadrupole Time-of-Flight Liquid Chromatography/Mass Spectrometry (Q-TOF LC/MS) system. Specific optical rotation was determined using Anton Paar MCP 500 polarimeter. Results: The parental compound (-)-swainsonine was successfully synthesized from D-isoascorbic acid through a 13-step process. Following published protocols, lactol-aldehyde tautomerism issue was encountered, leading to failure in obtaining precursor 8. We subsequently explored an alternative route and improved the access towards precursor 8 with few additional steps to prevent intramolecular cyclisation. Conclusion: In summary, we have succeeded in producing swainsonine skeleton from the inexpensive and readily available D-isoascorbic acid. While extending the number of steps involved, present modification led to improved accessibility to olefinic alcohol 8. [ABSTRACT FROM AUTHOR]

Introduction: 2,3-O-isopropylidene-D-erythrose has been a useful chiral precursor involved in the total synthesis of several natural products such as the leukotrienes, pyrrolizidine and indolizidine alkaloids. However, previous published protocols used expensive chemicals/reagents in the synthesis scheme. In this study, we synthesised D-erythrose from erythorbic acid with inexpensive and commercially available chemicals/reagents. Methods: D-erythrose was synthesised from published protocol with modification. Briefly, sodium erythorbate was treated with hydrogen peroxide to yield a mixture of D-erythronolactone, oxalic acid and sodium chloride. Further exposure to anhydrous acetone and p-toluenesulfonic acid monohydrate gave the acetonide form of D-erythronolactone. The corresponding acetonide was then partially reduced into the lactol in excellent yield by using sodium bis(2-methoxyethoxy-aluminium hydride. Purification of the products was carried out using the classical column chromatography Si-gel G60 (230-400 mesh, Merck). The 1H and 13C NMR spectra was registered in CDCl3 with Joel Resonance ECZ400S 400 MHz (1H) and 100 MHz (13C) using TMS as the internal standard. The specific optical rotation was determined using Anton Paar MCP 500 polarimeter. Results: 2,3-O-Isopropylidene-D-erythrose was obtained as colourless oil in the overall yield of 82% from the corresponding protected lactone. Conclusion: Selectively protected D-erythrose was easily prepared in substantial quantity as a mixture of enantiomers from the inexpensive chiral starting material. This may give a cheaper cost of production for clinically used drugs. [ABSTRACT FROM AUTHOR]

The title racemic oxopyrrolidine compound, C 13 H 17 NO 5 , contains three stereogenic centres and crystallizes with two mol-ecules in the asymmetric unit. The five-membered pyrrolidine rings in both mol-ecules exhibit envelope conformations. The N -ethyl group of one of the mol-ecules is disordered over two sets of sites in a 0.836 (4):0.164 (4) ratio. In the crystal, both mol-ecules form inversion dimers through pairwise O-H⋯O hydrogen bonds, generating R 2 2 (10) loops, which are linked into a three-dimensional network by weak C-H⋯O hydrogen bonds., (© Mohd Rosli et al. 2024.)

The asymmetric unit of the title compound, C 9 H 15 NO 4 , consists of a functionalized pyrrolidine ring having an envelope conformation, synthesized as an ethyl ester. The mol-ecule has three chiral centres and crystallized as a racemic mixture. In the crystal, mol-ecules are linked by pairwise O-H⋯O bonds, generating dimers with twofold rotational symmetry., (© Abdul id et al. 2023.)

The asymmetric unit of the title compound, C(14)H(17)NO(4)·1.25H(2)O, consists of four substituted pyrrolidone mol-ecules (two pairs of enanti-omers) and five water mol-ecules. The five-membered rings each have an envelope conformation, with the C atom bonded to the ester group as the flap. The mean planes of the five-membered rings of the four pyrrolidone mol-ecules make dihedral angles of 60.87 (5), 64.45 (5), 62.03 (5) and 65.79 (5)° with respect to the phenyl rings. In the crystal, the pyrrolidone and water mol-ecules are connected through O-H⋯O hydrogen bonds, forming a layer parallel to the ab plane. The two-dimensional network is further stabilized by inter-molecular C-H⋯O hydrogen bonds.

In the title compound, C(18)H(20)N(2)O(5), the pyrrolidine ring adopts an envelope conformation with the C atom bonded to the methyl groups as the flap. The dihydro-isoxazole ring is essentially planar (r.m.s. deviation = 0.041 Å) and forms a dihedral angle of 65.19 (6)° with the phenyl ring. In the crystal, neighbouring mol-ecules are linked into chains along [110] by inter-molecular C-H⋯O hydrogen bonds and weak C-H⋯π inter-actions involving the phenyl ring.