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Sharpless asymmetric dihydroxylation is an important reaction in the enantioselective synthesis of chiral vicinal diols that involves the treatment of alkene with osmium tetroxide along with optically active quinine ligand. Sharpless introduced this methodology after considering the importance of enantioselectivity in the total synthesis of medicinally important compounds. Vicinal diols, produced as a result of this reaction, act as intermediates in the synthesis of different naturally occurring compounds. Hence, Sharpless asymmetric dihydroxylation plays an important role in synthetic organic chemistry due to its undeniable contribution to the synthesis of biologically active organic compounds. This review emphasizes the significance of Sharpless asymmetric dihydroxylation in the total synthesis of various natural products, published since 2020. [ABSTRACT FROM AUTHOR]

An enantioselective total synthesis of novel gingerol-related compound 4-((3S,5R)-3,5-dihydroxynonadecyl)phenol, an anti-oxidant isolated from the resinous exudates of Chilean desert plants, has been accomplished from a known commercially available 4-(but-3-enyl) phenol by a concise ten-step sequence. In this synthesis, Sharpless asymmetric dihydroxylation, Grignard reaction and Iodine-induced electrophilic cyclization have been applied as key steps. [ABSTRACT FROM AUTHOR]

Eliglustat (Cerdelga®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral para-methoxycinnamyl benzyl ethers using chlorosulfonyl isocyanate as the key steps. Notably, the reaction between syn-1,2-dibenzyl ether 6 and chlorosulfonyl isocyanate in the mixture of toluene and hexane (10:1) afforded syn-1,2-amino alcohol 5 at a 62% yield with a diastereoselectivity > 20:1. This observation can be explained by competition between the SNi and the SN1 mechanisms, leading to the retention of stereochemistry. [ABSTRACT FROM AUTHOR]

We report a stereoselective total synthesis of a natural product, phomonol, from readily available D-aspartic acid. The key steps include Wittig olefination, Sharpless asymmetric dihydroxylation, Grignard addition, diastereoselective reductive etherification and Wacker oxidation. [ABSTRACT FROM AUTHOR]

Sharpless asymmetric dihydroxylation is an important reaction in the enantioselective synthesis of chiral vicinal diols that involves the treatment of alkene with osmium tetroxide along with optically active quinine ligand. Sharpless introduced this methodology after considering the importance of enantioselectivity in the total synthesis of medicinally important compounds. Vicinal diols, produced as a result of this reaction, act as intermediates in the synthesis of different naturally occurring compounds. Hence, Sharpless asymmetric dihydroxylation plays an important role in synthetic organic chemistry due to its undeniable contribution to the synthesis of biologically active organic compounds. This review emphasizes the significance of Sharpless asymmetric dihydroxylation in the total synthesis of various natural products, published since 2020.

A scalable synthesis of l - allo -enduracididine is achieved from commercially available (S)-glycidol in ten linear steps involving well-established synthetic transformations. The synthetic route is flexible and can be used to synthesize all four diastereomers by changing the stereochemistry of glycidol and Sharpless asymmetric dihydroxylation reagent. [ABSTRACT FROM AUTHOR]

Tetrahydropyrenophorol, an interesting macrodiolide, was isolated from the plant Fagonia cretica. The total synthesis of (–)-1-tetrahydropyrenophorol was achieved in an elegant and linear manner from readily an accessible racemic epoxide. The archetypal reactions include regioselective opening of the epoxide, Sharpless asymmetric dihydroxylation, and Mitsunobu cyclodimerization to construct the requisite 16-membered bis-lactone. The synthetic approach demonstrated here is very simple and could be used for the syntheses of related compounds in an economic and highly stereoselective way.

Eliglustat (Cerdelga®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral para-methoxycinnamyl benzyl ethers using chlorosulfonyl isocyanate as the key steps. Notably, the reaction between syn-1,2-dibenzyl ether 6 and chlorosulfonyl isocyanate in the mixture of toluene and hexane (10:1) afforded syn-1,2-amino alcohol 5 at a 62% yield with a diastereoselectivity > 20:1. This observation can be explained by competition between the SNi and the SN1 mechanisms, leading to the retention of stereochemistry.

An efficient enantioselective approach of Sacubitril 1 (a NEP inhibitor) which is used as a combination drug with Valsartan to treat heart failure, is described. The synthesis features the Evan's asymmetric alkylation, Sharpless asymmetric diydroxylation (AD) and Heck coupling reactions as key steps. [ABSTRACT FROM AUTHOR]

Flavan-3-ols are a series of natural products widely present in plants and show versatile biological activities. The structures of such compounds are characterized by owing two adjacent chiral centers and three rings. Their interesting structures and promising biological activities have driven increasing research developments toward the preparation of enantioenriched flavan-3-ols. This review summarizes the recent approaches for the asymmetric synthesis of chiral flavan-3-ols from two strategies in the construction of chiral centers. The key steps in the synthetic protocol involve Sharpless asymmetric dihydroxylation, Shi asymmetric epoxidation and Sharpless asymmetric epoxidation. [ABSTRACT FROM AUTHOR]

Abstract The de novo asymmetric total synthesis of (−)-nanaomycin A is described. The entirely linear route required only 13 steps from commercially available starting materials (3% overall yield). Key transformations include a Claisen rearrangement, an asymmetric dihydroxylation, a regioselective tosylation, a diastereoselective intramolecular Friedel-Crafts alkylation and a nitrile hydrolysis. As the route relies on a Sharpless asymmetric dihydroxylation it is equally amenable for the synthesis of (+)-nanaomycin A. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Sharpless asymmetric dihydroxylation of styrene derivative 6 afforded chiral triols (R)-7 and (S)-7, which were cyclized with tosyl chloride in the presence of Bu2SnO to provide 2-benzopyrans (R)-4 and (S)-4 with high regioselectivity. The additional hydroxy moiety in the 4-position was exploited for the introduction of various substituents. Williamson ether synthesis and replacement of the Boc protective group with a benzyl moiety led to potent σ1 ligands with high σ1/σ2-selectivity. With exception of the ethoxy derivative 16, the (R)-configured enantiomers represent eutomers with eudismic ratios of up to 29 for the ester (R)-18. The methyl ether (R)-15 represents the most potent σ1 ligand of this series of compounds, with a Ki value of 1.2 nM and an eudismic ratio of 7. Tosylate (R)-21 was used as precursor for the radiosynthesis of [18F]-(R)-20, which was available by nucleophilic substitution with K[18F]F K222 carbonate complex. The radiochemical yield of [18F]-(R)-20 was 18%–20%, the radiochemical purity greater than 97% and the specific radioactivity 175–300 GBq/µmol. Although radiometabolites were detected in plasma, urine and liver samples, radiometabolites were not found in brain samples. After 30 min, the uptake of the radiotracer in the brain was 3.4% of injected dose per gram of tissue and could be reduced by coadministration of the σ1 antagonist haloperidol. [18F]-(R)-20 was able to label those regions of the brain, which were reported to have high density of σ1 receptors.

Stereoselective syntheses of the 2,4,6-trideoxy-4-amino sugar d -vicenisamine and its epimers 3- epi - and 4- epi - d -vicenisamine were accomplished via stereoselective nitrogen functional group introduction and iodocyclization of carbamate. This versatile synthetic route started from the enantiomerically pure diol obtained from ethyl sorbate by Sharpless asymmetric dihydroxylation. [ABSTRACT FROM AUTHOR]

(3Z,9Z,6S,7R)-6,7-epoxy-3,9-octadecadiene (1) and (3Z,9Z,6R,7S)-6,7-epoxy-3,9-octadecadiene (2) have been stereoselectively synthesized in eight steps from 2-pentyn-1-ol with an overall yield of 8%. The key steps involved the Sharpless asymmetric dihydroxylation of (2E)-oct-2-en-5-yn-1-ol (6). The new synthetic method is suitable for multigram-scale preparation of 1 and 2 and might be used for producing sufficient quantities of the sex pheromone components for management of the pest of tea plantations. [ABSTRACT FROM AUTHOR]

Diastereoselective first total synthesis of parvistone C 1 and C8-epimer 1a are described. The key features of our synthesis include Sharpless asymmetric dihydroxylation, stereoselective aryl Grignard reactions, Still–Gennari olefination, and intramolecular cyclization. [ABSTRACT FROM AUTHOR]

An enantioselective synthesis of antidepressant drug (R)-(–)-venlafaxine is accomplished as an application of recently explored unusual Grignard reaction. An innovative method for the generation of chirality at extremely reactive benzylic center along with determination of absolute stereochemistry has been discussed. The key steps involved in the synthesis include Sharpless asymmetric dihydroxylation for the induction of chirality and an unusual Grignard reaction. [ABSTRACT FROM AUTHOR]

Symbiodinolide is a polyol marine natural product with a molecular weight of 2860. Herein, a streamlined synthesis of the C79–C97 fragment of symbiodinolide is described. In the synthetic route, a spiroacetalization, a Julia–Kocienski olefination, and a Sharpless asymmetric dihydroxylation were utilized as the key transformations.

Graphical abstract Highlights • First total synthesis of 14 membered 5′-hydroxyzearalenone has been achieved. • Starting material used are easily available 1,4-butane diol and propylene oxide. • Two chiral centers are created using well established protocols (Sharpless, Jocobsen). • Synthesis was achieved in 18 longest linear sequence with an overall yield of 3.6%. Abstract A first stereoselective total synthesis of 14-memebered β-resorcylic macrolactone 5′-hydroxyzearalenone (1) has been achieved. The key steps are Jocobsen hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylation, Vilsmeier-Haack reaction, Mitsunobu esterification and ring-closing metathesis. [ABSTRACT FROM AUTHOR]

Herein, we present the asymmetric synthesis of spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives as a new class of nonproteinogenic α-amino acid derivatives. Starting from commercially available 2-allylphenols, key β-hydroxy-α-amino esters were synthesized via high-yielding multi-step reaction sequences involving Sharpless asymmetric dihydroxylation as the chirality induction step. PhI(OAc) 2 -mediated oxidative dearomatization – spirocyclization of phenol-tethered β-hydroxy-α-amino esters efficiently produced the corresponding spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives, providing a general route to this hitherto-unreported class of compounds that are equipped with three privileged scaffolds (cyclohexadienone – tetrahydrofuran – α-amino ester). [ABSTRACT FROM AUTHOR]

A concise and enantioselective syntheses of antileukemic natural products such as (–)-(S)-goniothalamin and (–)-leiocarpin A has been accomplished in excellent yields. By employing reported conditions on suitable substrates via Julia–Kocienski olefination, intramolecular lactonization, and subsequently dehydroxylative olefination, (–)-(S)-goniothalamin was synthesized. Then Sharpless asymmetric dihydroxylation–intramolecular Michael addition on (–)-(S)-goniothalamin provided (–)-leiocarpin A. [ABSTRACT FROM PUBLISHER]

Asymmetric total synthesis of L-allo-1-deoxynojirimycin (L-allo-DNJ) was achieved from cis-butene-1,4-diol by employing Sharpless asymmetric dihydroxylation, stereoselective flash dihydroxylation and ring enlargement reactions as key steps. [ABSTRACT FROM AUTHOR]

An efficient total synthesis of (+)-petromyroxol, a marine natural product, is described. The synthesis utilizes the Sharpless asymmetric dihydroxylation (AD), intramolecular SN2 cyclization and stereoselective Grignard reaction as key steps. [ABSTRACT FROM AUTHOR]

A stereoselective formal total synthesis of the 20-membered marine macrolide Palmerolide A, a highly potent antitumor agent, is described. The key steps involved in this synthesis are reductive elimination, Sharpless asymmetric dihydroxylation, protecting group dependent ring-closing metathesis reaction, Sharpless asymmetric epoxidation, Takai olefination and macrolactonization via Heck coupling reaction. [ABSTRACT FROM AUTHOR]

Total syntheses of iso-cladospolide B ( 1) and the 12-membered macrolactone (6 S,12 R)-6-hydroxy-12-methyloxacyclododecane-2,5-dione ( 2), a non-natural product, were achieved from a common intermediate starting from commercially available 1,9-nonane diol. [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of two naturally occurring 5-hydroxy- γ-butyrolactones, (4 R,5 R)-5-hydroxy-4-decanolide ( 1a) and (−)-muricatacin ( 2), is described using a general alkyne-mediated strategy. The key steps involved are Sonogashira coupling for the desired carbon-chain extension followed by Sharpless asymmetric dihydroxylation to construct the hydroxy-lactone framework. [ABSTRACT FROM AUTHOR]

A straightforward synthesis of ( S)-gingerols 1- 3 has been described. The requisite stereogenic center in the target molecules was introduced by Sharpless asymmetric dihydroxylation using a chiral complex, AD-mix β. This route is simple and efficient to prepare the products in very good yields. [ABSTRACT FROM AUTHOR]

An efficient, short and convenient asymmetric synthesis of ( R )-(+)-lipoic acid in seven steps from chiral hydroxy aldehyde with 32.5% overall yield is described. Synthesis of S and R enantiomers of α-lipoic acid from cis -1,4-butene diol derived chiral lactone is reported with 34 % overall yield. The present synthesis involves use of simple reaction conditions making it a convenient synthesis. [ABSTRACT FROM AUTHOR]

A straightforward strategy for the stereoselective synthesis of (+)-bovidic acid has been developed in eleven steps with an overall yield of 8.85%. The synthesis started from commercially available nonanal, and the key reactions involved were Sharpless asymmetric dihydroxylation, Grignard reaction, and CoreyBakshiShibata reduction. [ABSTRACT FROM AUTHOR]

A stereoselective synthetic route has been developed toward the synthesis of novel γ-substituted pantolactone homologues using Sharpless asymmetric dihydroxylation of the enantiomeric alkene–ester intermediates, derived from ( R )-glyceraldehyde acetonide, as the key step. [ABSTRACT FROM AUTHOR]

The first concise stereoselective total synthesis of diarylheptanoid rhoiptelol C ( 1) was achieved from readily available vanillin. The synthesis involves Keck's asymmetric allylation, olefin cross metathesis, and Sharpless asymmetric dihydroxylation reaction as key steps. [ABSTRACT FROM AUTHOR]