Application of RCM reaction in the construction of ABC ring of micrandilactone A.

[reaction: see text] The functionalized ABC ring system of micrandilactone A was successfully constructed in 14 steps. The key reactions in this synthesis are the intermolecular Diels-Alder reaction (IMDA) and the eneyne ring-closing metathesis (RCM) reaction.

Total synthesis of (±)-decinine via an oxidative biaryl coupling with defined axial chirality.

The total synthesis of (±)-decinine has been achieved. The key steps in the synthesis involved the formation of lasubine II via a gold catalyzed annulation of 1-(but-3-yn-1-yl)piperidine and the formation of the 12-membered ring of decinine (1) with complementary atropselectivity via a VOF3-mediated oxidative biaryl coupling reaction.

Diastereoselective total synthesis of (±)-schindilactone†A, Part†1: Construction of the ABC and FGH ring systems and initial attempts to construct the CDEF ring system.

First-generation synthetic strategies for the diastereoselective total synthesis of schindilactone A (1) are presented and methods for the synthesis of the ABC, FGH, and CDEF moieties are explored. We have established a method for the synthesis of the ABC moiety, which included both a Diels-Alder reaction and a ring-closing metathesis as the key steps. We have also developed a method for the synthesis of the FGH moiety, which involved the use of a Pauson-Khand reaction and a carbonylative annulation reaction as the key steps. Furthermore, we have achieved the construction of the central 7-8 bicyclic ring system by using a [3,3]-rearrangement as the key step. However, unfortunately, when this rearrangement reaction was applied to the construction of the more advanced CDEF moiety, the anticipated annulation reaction did not occur and the development of an alternative synthetic strategy would be required for the construction of this central core.

Diastereoselective total synthesis of (±)-schindilactone†a, Part†3: The final phase and completion.

The final phase for the total synthesis of (±)-schindilactone A (1) is described herein. Two independent synthetic approaches were developed that featured Pd-thiourea-catalyzed cascade carbonylative annulation reactions to construct intermediate 3 and a RCM reaction to make intermediate 4. Other important steps that enabled the completion of the synthesis included: 1) A Ag-mediated ring-expansion reaction to form vinyl bromide 17 from dibromocyclopropane 30; 2) a Pd-catalyzed coupling reaction of vinyl bromide 17 with a copper enolate to synthesize ketoester 16; 3) a RCM reaction to generate oxabicyclononenol 10 from diene 11; 4) a cyclopentenone fragment in substrate 8 was constructed through a Co-thiourea-catalyzed Pauson-Khand reaction (PKR); 5) a Dieckmann-type condensation to successfully form the A ring of schindilactone A (1). The chemistry developed for the total synthesis of schindilactone A (1) will shed light on the synthesis of other family members of schindilactone A.

Synthesis and antitumor activity of simplified ecteinascidin-saframycin analogs.

Two series of simplified analogs of the ecteinascidin-saframycin type alkaloids were prepared from l-DOPA. Their in vitro antitumor activity was tested against three human cancer cell lines (HCT-8 colon carcinoma, Bel-7402 liver carcinoma, and BGC-823 gastric carcinoma). Among these compounds, the ester analogs have stronger activities than those of amide analogs in general. Among them, 1-naphthalene carboxylate ester analog 31 has the strongest activity against BGC-823 cells.