Sintese total de (+)-cularina, (+)-sarcocapnina, (+)-sarcocapnidina (+)-crassifolina

AUTOR(ES)
DATA DE PUBLICAÇÃO

1994

RESUMO

The alkaloid (+)-cularine was isolated by Manske in 1938 from plants belonging to the genera Dicentra and Corydalis. Two altemative synthetic convergent routes were proposed by us to obtain the (±)-didehydronorcularine 290 and (±)-didehydronorisocularine 309 in the key step. The iminophosphorane 244 was prepared by a Staudinger reaction in 95% yield, or by a Mitsunobu procedure in 98% yield. After condensing the iminophosphorane 244 and the ketene 267 via an aza-Wittig reaction in toluene at 76°C/14 hs, we isolated 1-benzyl-3,4- dihydroisoquinolines 278a,278c e 278d in 76%, 78% and 60% yields, respectively. After debromination of 278a with butyllithium and debenzylation, we obtained 284 in 83% yield A remote intramolecular cyclization with NaH and then with C6F5I(OCOCF3)2 gave the (±)-didehydronorcularine 308 (para coupling) in 36% yield and (±)-didehydronorisocularine 309 (ortho coupling) in 58% yield, probably through an oxenium ion intermediate The cularine 1a was aIso prepared starting with the nitro-derivative 292 which was reduced to an amine in 88% yield and then diazotized in presence of sodium azide to give 294 in 83% yield This azide was submited to a remote intramolecular cyclisation with triflic acid (-10°C) to give the (±)-aminodidehydronorcularine 297 in 81% yield Diazotization of (±)-297 gave the (±)-didehydronorcularine 290 in 81% yield which was treated with (+)-8- phenylmenthyl chloroacetate in methanol overnight and then with sodium borohydride to give (+)-O-demethylcularine 1b in 95% yield, mp 127-128°C (lit 126-127°C), [a]D25 +323,5° Reaction of (+)-1b with diazomethane gave (+)- cularinea 1a, mp 114-115°C (lit 115°C), [a]D25 +283,8° (lit +285°) The reductive methylation of (±)-309 by the same procedure used for (±)-290, gave (+)- sarcocapnidine 2b in 93% yield, mp 125-126°C (Iit 126-127°C),[a]D25 +384° (+385,4°) Methylation of(+)-2b with diazomethane gave (+)-sarcocapnine 2a in 97% yield as an oil, which was crystallized as bydrochloride, mp 212-213°C (lit 213-215°C), [a]D25 +217° (lit 218°).

ASSUNTO(S)

alcaloides sintese organica

ACESSO AO ARTIGO

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