Applications of sharpless asymmetric dihydroxylation in the total synthesis of natural products

Sharpless asymmetric dihydroxylation involves the reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form an optically active vicinal diol. This reaction was primarily developed by Sharpless based on the already known racemic Upjohn dihydroxylation. The chiral diols obtained by Sharpless asymmetric dihydroxylation are important intermediates in organic synthesis. Herein, we emphasise the applications of Sharpless asymmetric dihydroxylation in the total synthesis of natural products.     

Stereoselective synthesis of (+)-boronolide

An efficient enantio- and stereocontrolled total synthesis of (+)-boronolide from valeraldehyde is described. The key steps include a Sharpless asymmetric dihydroxylation, a chelation controlled Grignard reaction followed by Sharpless asymmetric epoxidation and a ring closing metathesis.     

Total synthesis of the proposed structure of xylarolide

A total synthesis of a proposed structure of xylarolide is described. The key features of the synthesis include Sharpless asymmetric reaction, Wittig olefination, Sharpless asymmetric dihydroxylation, Still-Gennari olefination and Yamaguchi lactonization. The differences in the spectroscopic data of the synthetic and natural product indicate a revision of the assigned structure.     

The first stereoselective and the total synthesis of Leiocarpin C and total synthesis of (+)-Goniodiol

The synthesis of the styryl lactone Leiocarpin C has been achieved in a highly stereoselective manner using Jacobsen’s kinetic resolution, Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation as key steps. This is the first total synthesis of Leiocarpin C, and thus establishes for the first time the absolute stereochemistry of this natural product.     

Asymmetric Synthesis of Chiral Flavan-3-Ols

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.     

Olefin cross-metathesis based approach for the stereoselective total synthesis of (+)-cardiobutanolide

Olefin cross-metathesis approach to (+)-cardiobutanolide has been achieved starting from d-mannitol utilizing Sharpless kinetic resolution and Sharpless asymmetric dihydroxylation.     

Highly stereoselective synthesis of antitumor agents: both enantiomers of goniothales diol,altholactone, and isoaltholactone

A flexible stereoselective route to synthesize both enantiomers of the highly functionalized substituted tetrahydrofurans and α,β-unsaturated-δ-lactones, goniothales diol, altholactone, and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulfonic acid.     

A concise and stereoselective synthesis of both enantiomers of altholactone and isoaltholactone

A concise and flexible stereoselective route to synthesize both enantiomers of the highly functionalized α,β-unsaturated-δ-lactones, altholactone and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulphonic acid.     

First stereoselective total synthesis of antibiotic macrolide Berkeleylactone F

The first stereoselective total synthesis of antibiotic macrolide Berkeleylactone F is described. The synthetic sequence notably features Sharpless kinetic resolution to access chiral epoxide followed by its regioselective ring-opening reaction, Sharpless asymmetric reaction and ring-closing metathesis.     

Stereoselective total synthesis of (+)-boronolide

A seteroselective total synthesis of (+)-boronolide is described. The key steps are Sharpless asymmetric dihydroxylation, Shibasaki's asymmetric Henry reaction, asymmetric allylation and ring closing metathesis.     

Asymmetric total syntheses of spisulosine, its diastereo- and regio-isomers

Starting from palmityl alcohol, divergent stereoselective syntheses of spisulosine and its diastereo- and regio-isomers have been achieved. In the Sharpless asymmetric dihydroxylation-based approach, the key step is the synthesis of monoprotected diol, whereas Miyashita’s boron-directed C-2 regioselective azidolysis of enantiomerically pure epoxy alcohol is the vital step in the Sharpless asymmetric epoxidation-based route. The latter approach involves the first protecting-group-free synthesis of spisulosine.     

Studies directed toward the total synthesis of azaspiracid: stereoselective construction of C(1)-C(12), C(13)-C(19), and C(21)-C(25) fragments

[reaction: see text] The efficient entry to the C(1)-C(12), C(13)-C(19), and C(21)-C(25) fragments of azaspiracid is outlined. The C(1)-C(12) portion is constructed using a key asymmetric allenyl borane addition to the corresponding alpha,beta-unsaturated aldehyde. The synthesis of the C(13)-C(19) portion utilizes an Evans asymmetric alkylation followed by Sharpless asymmetric dihydroxylation. In addition, a novel solution to the mismatched effects of a neighboring chiral oxazolidinone during a Sharpless dihydroxylation is detailed.     

Stereoselective total synthesis of (+)-anamarine via cross-metathesis protocol

A convergent stereoselective total synthesis of (+)-anamarine via cross-metathesis (CM) protocol starting from 2-butyn-1,4-diol and vinyl lactone is reported. Other key features of the strategy include the use of Sharpless asymmetric epoxidation, Sharpless dihydroxylation, and Red-Al reduction.     

Asymmetric synthesis of (+)-tetrahydropseudodistomin

An efficient asymmetric synthesis of (+)-tetrahydropseudodistomin is described. The important synthetic features include a Maruoka asymmetric allylation and a Sharpless asymmetric dihydroxylation as key steps for the generation of chirality at C-2, -4, and -5 of the trisubstituted piperidine ring.     

Enantioselective synthesis of (−)-α-conhydrine via cyclic sulfate methodology

An asymmetric synthesis of (−)-α-conhydrine is described using the Sharpless asymmetric dihydroxylation and the regiospecific nucleophilic opening of a cyclic sulfate as the key steps.     

Enantioselective synthesis of (R)-(−)-mevalonolactone via cyclic sulfate methodology

An asymmetric synthesis of (R)-(−)-mevalonolactone is described using the Sharpless asymmetric dihydroxylation and the regioselective nucleophilic opening of a cyclic sulfate as key steps.     

Stereoselective synthesis of bis-hydroxy-tetrahydrofurans using cross metathesis

A short asymmetric approach for the synthesis of bis-tetrahydrofuran units of various annonaceous acetogenins is described. The key steps of the synthesis are self-cross metathesis and Sharpless asymmetric dihydroxylation.     

有机硅化合物的不对称合成反应

介绍了“碳中心”手性有机硅化合物的合成,以及在烯丙基硅烷与醛的Hosomi-Sakurai反应和α-烯丙基硅碳负离子与醛的反应中的应用。提出并实践了两条提高对映选择性的途径。烯基硅醇的不对称环氧化反应扩展了Sharpless反应的适用范围,为合成光活性的具简单结构的环氧化合物提供了一条简易的途径。     

Stereo selective synthesis of C3–C12 fragment of iriomoteolide-1a

A convergent and flexible synthetic route for the synthesis of C3–C12 fragment of iriomoteolide-1a is described. The key steps are: Mannich reaction, Keck asymmetric allylation, Sharpless asymmetric epoxidation and cross-metathesis protocol.     

Asymmetric total synthesis of (+)-cardiobutanolide via an iterative asymmetric dihydroxylation in PEG

The stereoselective total synthesis of (+)-cardiobutanolide, a polyhydroxylated natural product, is achieved in high yield through Lu and Guo diene synthesis, Sharpless asymmetric dihydroxylation, and one-pot deprotection-lactonization. The utility of a recyclable reagent system in PEG for asymmetric dihydroxylation is demonstrated.