Assuntos
Complemento C5a/metabolismo , Depsipeptídeos/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Mastócitos/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Depsipeptídeos/química , Cobaias , Humanos , Mastócitos/metabolismo , Estrutura Molecular , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Peptídeos/química , RatosRESUMO
[reaction--see text] An 18-step asymmetric synthesis of the bryostatin 1 "southern hemisphere" fragment (1) has been developed. Key steps include an aldol reaction between 6 and 7 and a dehydration to establish the (E)-exocyclic alkene in 2 and a stereoselective Luche reduction and protection with TESOTf to access 1.
Assuntos
Antibacterianos/síntese química , Antibióticos Antineoplásicos/síntese química , Lactonas/síntese química , Briostatinas , Indicadores e Reagentes , Macrolídeos , Espectroscopia de Ressonância Magnética , EstereoisomerismoRESUMO
[reaction: see text]. An efficient [2 + 2 + 2]-fragment condensation strategy is described for obtaining the cyclodepsipeptide core of verucopeptin. The 19-membered macrocycle was established through a Carpino HATU mediated macrolactamization, which proceeded in good yield under high-dilution conditions.
Assuntos
Antibióticos Antineoplásicos/síntese química , Depsipeptídeos , Peptídeos Cíclicos/síntese química , Antibióticos Antineoplásicos/química , Peptídeos/química , Peptídeos Cíclicos/químicaRESUMO
A completely stereocontrolled asymmetric synthesis of an advanced B-ring synthon for the bryostatin family of antitumor agents is reported. Noteworthy features of our synthesis include the Smith-Tietze bis-alkylation reaction between 12 and 13 en route to C(2)-symmetrical ketone 10 and the totally stereoselective conversion of 10 into triol 18 via a Grignard addition tactic. Triol 18 was converted to epoxide 3 in nine steps, and an acid-catalyzed intramolecular Williamson etherification reaction completed the synthesis of 2.
