Ai-E Wang

Direct Transformation of Secondary Amides into Secondary Amines: Triflic Anhydride Activated Reductive Alkylation

National Basic Research Program (973 Program) of China [2010CB833200]; NSF of China [21072160, 20832005]; Fundamental Research Funds for the Central Universities of China [201112G001]; Ministry of Education of China

A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A

By using a methyl tetramate derivative (R)- or (S)-9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)- or (S)-5-alkyltetramates (2) is disclosed. Among the synthesized methyl 5-alkyltetramates 2, methyl 5-methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5-benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)-9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)-belamide A (7) been confirmed, but also the solvent used for recording the (13) C NMR spectrum, the (13) C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised.

Complexity generation by chemical synthesis: a five-step synthesis of (−)-chaetominine from L-tryptophan and its biosynthetic implications

We demonstrated, for the first time, that on the basis of chemistry principles, the hexacyclic peptidyl alkaloid (−)-chaetominine (1) can be synthesized in a straightforward manner from L-Trp. The approach features the efficient generation of molecular complexity via a tandem C3/C14 syn-selective epoxidation (dr = 3:2)–annulative ring-opening reaction and a regioselective epimerization at C14. The successful production of (−)-chaetominine (1) from L-Trp could be helpful for revealing how the configuration of L-tryptophan becomes inverted in the biosynthetic pathway of (−)-chaetominine (1).

Concise Asymmetric Total Synthesis of 9-epi-Sessilifoliamide J

A 10-step asymmetric synthesis of 9-epi-sessilifoliamide J (20), together with sessilifoliamide J (6), has been accomplished from the key chiral building block 11 via a threo-selective vinylogous Mannich reaction and a Ley oxidation-SmI(2)-mediated coupling lactonization. The absolute configuration of the natural sessilifoliamide J was established.

SmI2-Mediated Radical Coupling Strategy to Securinega Alkaloids: Total Synthesis of (−)-14,15-Dihydrosecurinine and Formal Total Synthesis of (−)-Securinine

The asymmetric total synthesis of (-)-14,15-dihydrosecurinine and the formal total synthesis of (-)-securinine were accomplished starting from an easily available malimide. A concise SmI2-mediated radical coupling strategy has been developed to construct the bridged α-hydroxy 6-azabicyclo[3.2.1]octanone in four steps with high diastereoselectivity.

Titanocene(III)-Catalyzed Three-Component Reaction of Secondary Amides, Aldehydes, and Electrophilic Alkenes

An umpolung Mannich-type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one-pot formation of C-N and C-C bonds by a titanocene-catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N-substituted γ-amido-acid derivatives and γ-amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α-amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.

Efficient asymmetric syntheses of alkaloids and medicinally relevant molecules based on heterocyclic chiral building blocks

Abstract In this report, we present recent progress in synthetic methodologies based on three heterocyclic chiral building blocks developed from our laboratories. The potential of these chiral building block-based methods in the concise asymmetric synthesis of alkaloids and medicinally interesting molecules has been demonstrated by the total syntheses of 8-aza-prostaglandin E1, 11-hydroxylated analogues of the lead compounds CP-734432 and PF-04475270, (+)-castanospermine, (+)-1-epi-castanospermine, 7-deoxy-6-epi-castanospermine as well as 9-epi-sessilifoliamide J.

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.

General and Chemoselective Bisphosphonylation of Secondary and Tertiary Amides

With Tf2O as the activation reagent, a mild and general method has been developed for the bisphosphonylation of both secondary and tertiary amides. The protocol is highly efficient and chemoselective, and it tolerates a number of sensitive functional groups such as cyano, ester, and aldehyde groups.

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1] nonan-3-ones is presented. Using keto-lactams as the starting materials, this two-step method consists of silyl enol ether formation with TBDMSOTf, lactam activation with Tf2O/DTBMP, and halide-promoted cyclization. Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones, which can be hydrogenated to yield 3α,6β-dihydroxytropanes. Starting from optically active keto-lactams, the method has been applied to the enantioselective syntheses of (+)-(1S,3S,5R,6S)-pervilleine C (6), (+)-(1S,3R,5S,6R)-valeroidine (3), (+)-(1S,3S,5R,6S)-dibenzoyloxytropane (8), and (+)-(1S,3S,5R,6S)-merredissine (9).