Toward the total synthesis of natural peloruside a: stereoselective synthesis of the backbone of the core

[reaction: see text] An asymmetric synthesis of the backbone of the core of natural peloruside A is described. Key elements include reiterative application of enantioselective allylation to establish the stereochemistry of the backbone and a double asymmetric aldol reaction to successfully couple two fragments.     

Asymmetric total synthesis and formal total synthesis of the antitumor sesquiterpenoid (+)-eremantholide A

[structure: see text]. A new asymmetric total synthesis of (+)-eremantholide A is reported in which a Hoveyda-Grubbs ring-closing metathesis (RCM) reaction is used to assemble the nine-membered oxonin ring, and an enolate alkylation between the 3(2H)-furanone 2 and O-triflate 3 is exploited for C(9)-C(10) bond construction. An Evans asymmetric aldol reaction and a Sharpless asymmetric epoxidation served to stereoselectively install the C(6), C(7), and C(8) stereocenters of the target structure.     

Versatile asymmetric synthesis of the kavalactones: first synthesis of (+)-kavain

[reaction: see text] Three asymmetric pathways to the kavalactones have been developed. The first method is chiral auxiliary-based and utilizes aldol reactions of N-acetyl thiazolidinethiones followed by a malonate displacement/decarboxylation reaction. The second approach uses the asymmetric catalytic Mukaiyama additions of dienolate nucleophile equivalents developed by Carreira and Sato. Finally, tin-substituted intermediates, prepared by either of these routes, can serve as advanced general precursors of kavalactone derivatives via Pd(0)-catalyzed Stille couplings with aryl halides.     

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.     

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.     

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 synthesis of 3-substituted isoindolinones: application to the total synthesis of (+)-lennoxamine

An anionic chiral auxiliary mediated asymmetric alkylation of carbamate 2 provides 3-substituted isoindolinones 4 in high ee. This methodology was used in the first asymmetric synthesis of (+)-lennoxamine.     

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.     

Asymmetric synthesis of the ab-ring of aklavinone

A formal synthesis of the AB-ring of aklavinone 3 was achieved via the asymmetric synthesis of diol 8 prepared in three steps from tetralone 5. The crucial step involved the asymmetric hydroxylation of 5 in ≥ 95% ee using (camphorylsulfonyl)oxaziridine derivative (+)-4b.     

Asymmetric synthesis of fagomine

We report an asymmetric synthesis of the alkaloid fagomine, which is an inhibitor of mammalian α-glucosidase and β-galactosidase, by means of Sharpless asymmetric dihydroxylation and Pd(II)-catalyzed cyclization, starting from 3-(t-butoxylcarbonylamino)propanol.     

Asymmetric catalytic synthesis of the proposed structure of trocheliophorolide B

A concise catalytic asymmetric synthesis of the proposed structure of trocheliophorolide B is reported. The synthetic sequence notably features an asymmetric acetaldehyde alkynylation, a Ru-catalyzed alder-ene reaction, and a Zn-ProPhenol ynone aldol condensation. Comparison with the reported data suggests a misassignment of the natural product structure.     

Asymmetric synthesis of the highly methylated tryptophan portion of the hemiasterlin tripeptides

[reaction: see text] The asymmetric synthesis of the methylated tryptophan portion of hemiasterlin peptides is described. The key reactions are a SnCl4-mediated ring opening of epoxynitriles or epoxysulfones by N-methylindole followed by an asymmetric Strecker reaction. A second approach involving opening of glycidic esters by indoles is also described.     

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.     

Catalytic asymmetric synthesis of 1,4-enynes

1,4-Enyne units are ubiquitous skeletons in biologically active molecules and natural products. Especially, they represent versatile building blocks for abundant downstream derivatizations via controllable modifications of both alkene and alkyne units independently. Recently, great efforts have been made to establish efficient protocols to achieve optically active 1,4-enynes. Considering the enormous application potential of enantioenriched 1,4-enyne units but no related review on this topic has been described, here we aim to provide a comprehensive summary on the catalytic methods established for enantioselective constructions of these intriguing skeletons. According to the reaction types, this review is divided into five parts, including asymmetric allylic substitution, asymmetric propargylic substitution, asymmetric alkynylallylic substitution, asymmetric hydroalkynylation and asymmetric 1,2-addition of alkynes to conjugated imines or ketones.     

Development of new methods in organic synthesis and their applications to the synthesis of biologically interesting natural products

2,6-Dimethyl-9-Aryl-9-phosphabicyclo[3.3.1]nonanes (9-PBN and 9-NapBN) and the chiral diaminophosphine oxides (DIAPHOXs) derived from aspartic acid have been introduced as useful ligands and preligands, respectively, for transition metal-catalyzed asymmetric synthesis. anti-Selective asymmetric hydrogenation of α-amino-β-ketoesters using Ru-, Rh-, Ir-, and Ni-catalysts through dynamic kinetic resolution have been developed for the first time, producing efficiently important anti β-hydroxy-α-amino acids. The total synthesis of several biologically active natural products was achieved by use of the transition metal-catalyzed reaction using DIAPHOX, anti-selective asymmetric hydrogenation, and reactions developed by us. Synthesis of tangutorine, an antitumor indole alkaloid, has been enantioselectively achieved for the first time. Enantioselective synthesis of a martinelline chiral core was accomplished using the asymmetric tandem Michael-Aldol reaction as a key step developed by us. This synthesis represents the formal total synthesis of martinelline and martinellic acid. Papuamide B was synthesized through the elucidation of unknown stereostructures by using the anti-selective asymmetric hydrogenation and reactions developed by us.     

Asymmetric total synthesis of antiochic acid

The first asymmetric total synthesis of antiochic acid using bioinspired polyene cyclization strategy is described. Both good yield and good asymmetric induction were obtained.     

Stereoselective synthesis of the macrolactone core of (+)-neopeltolide

A stereoselective synthesis of the macrolactone core of the potent anticancer agent neopeltolide is disclosed. The key steps of the synthesis include asymmetric allylation using Krische' protocol, conjugate reduction using MacMillan's methodology, and an asymmetric hetero-Diels-Alder reaction using Jacobsen's catalyst. Substrate controlled diastereoselective 1,3-anti reduction of a keto alcohol, Luche reduction followed by Ireland-Claisen rearrangement, oxymercuration, and reductive lithiation are other key steps.     

固态"绝对"不对称合成

光学活性生物分子的形成是世界进化历史中一个重要过程。"绝对"不对称合成, 即在没有任何外界手性诱导试剂作用下或在圆偏振光影响下的封闭体系中的不对称合成, 为前生物时期天然手性的成因提供了解释。本文将综述通过非手性分子形成的手性晶体的固相反应进行的"绝对"不对称合成。     

De novo synthesis of natural products via the asymmetric hydration of polyenes

For the last ten years our group has been working toward the development of an asymmetric hydration approach to polyketide natural products based on the regioselective hydration of di- and tri-enoates. Key to the success of this approach is the recognition that both high regiocontrol and asymmetric induction could be obtained by the use of a Sharpless asymmetric dihydroxylation reaction. Herein we describe the development of the method and its application to natural product total synthesis.     

Stereoselective synthesis of (+)-hyptolide

The first total synthesis of the naturally occurring lactone (+)-hyptolide is described. Ethyl l-lactate was the chiral starting material. Key steps of this 15-step synthesis were a Brown's asymmetric allylation, a Carreira's asymmetric ethynylation and a ring closing metathesis.