A Convergent Synthesis of the Macrocyclic Core of Cytotrienins:  Application of RCM for Macrocyclization

Abstract

[reaction: see text] The asymmetric synthesis of the fully elaborated macrocyclic core of cytotrienins A-D, potent apoptosis-inducing agents, is described. Synthetic highlights include the construction of the aniline bond using a copper-mediated amidation and the use of a ring-closing metathesis (RCM) reaction to efficiently install the (E,E,E)-triene and simultaneously construct the macrocyclic lactam.

Synthesis and evaluation of 5′-modified thymidines and 5-hydroxymethyl-2′-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors

“…Diethyl ((methylsulfonyl)methyl)phosphonate 6 was prepared according to known procedures [7], while Horner reagent 9 was obtained by reacting half an equivalent of chlorodiethylphosphate with bis-lithiated 8 [8,9]. 3'-Silylated thymidine 12 was produced by a selective cleavage of the primary TBDMS group on 11 [10,11].…”

“…The filtrate was concentrated and the residue purified by flash column chromatography (8)(9)(10)(11)(12) % MeOH + 0.5% HCOOH in CH 2 Cl 2 ) to afford 47 as a white solid (45 mg, 87%). 1 H NMR…”

Metátese de olefinas aplicada ao fechamento de anéis: uma ferramenta poderosa para a síntese de macrociclos naturais

“…A escolha do bom catalisador para realizar macrociclizações, particularmente nos casos mais complexos, onde várias ligações duplas tendem a competir pela complexação com o metal, pode ser ilustrada pela síntese da unidade macrocíclica central das citotrieninas, lactamas naturais de 21 membros obtidas por fermentação de fungos do gênero Streptomyces, por Panek e colaboradores (Esquema 7) 42 . 4 decorrente da iniciação da reação de RCM a partir de uma das ligações duplas internas do substrato.…”

A Symmetry‐Based Synthesis of the Heterobicyclic Core of the Zaragozic Acids/Squalestatins

“…The smooth two-fold AD transformation fortunately observed for 9 in contrast to the model substrate [5b] can probably be rationalized with a better solubility of the diol intermediate produced from 9 in the organic layer. Use of isopropylmagnesium chloride [14] allowed a chemoselective exchange of the ester functions against Weinreb amides, whereupon the resulting product 12 was converted into diketone 14 with the lithium species [15] derived from 13. At this point, it proved advisable to mask the two carbonyl groups temporarily as protected alcohols in order to prevent undesired cyclizations in the course of the furan oxidation.…”