Partial reduction of pyrroles: application to natural product synthesis

The partial reduction of N-Boc pyrroles has been explored giving stereoselective routes to disubstituted pyrrolines in good yields and with excellent diastereoselectivities. A novel methodology has been developed to carry out reductive aldol reactions on 2-substituted N-Boc pyrroles; use of aldehydes under reductive aldol conditions gave the anti aldol product in good selectivity. This chemistry was used as the key transformation in a synthesis of omuralide, which was achieved in 13 steps and 14% overall yield. We also report a methodology for selectively forming either cis or trans 2,5-disubstituted pyrrolines via a partial reduction of an electron-deficient N-Boc pyrrole. The trans pyrroline formed using this route was utilized in the syntheses of the polyhydroxylated pyrrolizidine natural products hyacinthacine A1 and 1-epiaustraline. Further investigation has led to the development of routes to enantiopure substituted pyrroline compounds. This has been achieved via a chiral protonation approach using easily accessible chiral acids, such as ephedrine and oxazolidinones, to quench enolates formed during the partial reduction process. Alternatively, enzymatic desymmetrization of symmetrical diol compounds formed from the partial reduction products of substituted pyrroles is also reported. This leads to formation of both enantiomers of 2,2- and 2,5-disubstituted N-Boc pyrrolines in excellent ee and yields.     

Biomimetic total synthesis of (+)-gelsemine

Challenging: (+)-gelsemine was synthesized from (R,R)-aziridine 1 in 25 steps with approximately 1 % overall yield. A multistep, one-pot enol-oxonium cyclization cascade was used to construct, simultaneously, the E ring, F ring, C3 stereocenter, and C7 quaternary stereocenter. This synthesis using the enol-oxonium cyclization reaction as a key step to make the cage structure has demonstrated the proposed biosynthetic pathway of the gelsemine family.     

Norrisolide: total synthesis and related studies

A stereoselective synthesis of (+)-norrisolide is presented. This natural product belongs to a family of marine spongiane diterpenes the structure of which is characterized by a fused gamma-lactone-gamma-lactol ring system attached to a bicyclic hydrophobic core. Our studies led to the development of a expedient synthesis of such gamma-lactone-gamma-lactol motifs based on ring expansion of a fused cyclopropyl ester. Highlights of the synthetic strategy toward norrisolide include the coupling of the two bicyclic systems by constructing a sterically demanding C9-C10 bond and the installation of the C19 oxygen at the last step of the synthesis via a Baeyer-Villiger oxidation.     

Progress on the total synthesis of natural products in China: From 2006 to 2010

This paper summarizes the progress on the total syntheses of natural products accomplished in mainland China during the period from 2006 to 2010.The overview focuses on the first total synthesis of natural products of contemporary interest including alkaloids,cyclopeptides and cyclic depsipeptides,macrolides,terpenoids and steroids,saponins and glycosides.The development of novel synthetic strategies and methodologies,and application of new selective synthetic methods in the total syntheses of natural products are included as well.     

Actin-binding marine macrolides: total synthesis and biological importance

Marine organisms produce a fascinating range of structurally diverse secondary metabolites, which often possess unusual and sometimes unexpected biological activities. This structural diversity makes these marine natural products excellent molecular probes for the investigation of biochemical pathways. Recently, a number of novel and stereochemically complex macrolides, having a large macrolactone (22- to 44-membered) ring, that interact with the actin cycloskeleton have been isolated from different marine sources. Actin, like tubulin, is a major component of the cytoskeleton and has important cellular functions. Although the details of these interactions are still under investigation, these marine macrolides are becoming increasingly important as novel molecular probes to help elucidate the cellular functions of actin. Owing to their potent antitumor activities, these compounds, for example the aplyronines, also have potential for preclinical development in cancer chemotherapy. Their appealing molecular structures, with an abundance of stereochemistry, and biological significance, coupled with the extremely limited availability from the marine sources, have stimulated enormous interest in the synthesis of these compounds. This review summarizes the biological properties of these unusual marine natural products and features the recently completed total syntheses of swinholide A, scytophycin C, aplyronine A, mycalolide A--all of these being potent cytotoxic agents that target actin--and a diastereoisomer of ulapualide A. Rather than detailing each individual step of these multistep total syntheses, the different synthetic strategies, key reactions, and methods adopted for controlling the stereochemistry are compared.