RESUMO
Treatment of 1-(2'-bromo-3',4'-dialkoxybenzyl)-1,2,3, 4-tetrahydroisoquinoline carbamates, 1a,c, with excess alkyllithium gave 8-oxoberbines, 2a,c, which were successively attacked in situ with another molecule of alkyllithium to give 1,2 and/or 1,4 addition products. A primary alkyllithium, such as MeLi or BuLi, gave a 1,2 addition product, 8-methyleneberbine 9a or 8-butylideneberbine 3a. t-BuLi preferred 1,4 addition, followed by elimination of the alkoxy group, to give 9-tert-butyl-8-oxoberbine 6a or 7c. s-BuLi gave a mixture of 1,2 and 1,4 addition products, 1-[2'-(2' '-methylbutyryl)benzyl]-1,2,3,4-tetrahydroisoquinoline 4a and 9-s-butyl-8-oxoberbine 5a. Similar treatments of carbamate 1b having no alkoxy group at its 3' position gave 1,2 addition products, 8-butylideneberbine 3b, 1-[2'-(2' '-methylbutyryl)benzyl]-1,2,3, 4-tetrahydroisoquinoline 4b, and 1-(2'-pivaloylbenzyl)-1,2,3, 4-tetrahydroisoquinoline 6b, in all cases. Reactions of 1a with s-BuMgCl and isoPrMgCl also gave the 1,4 adduct, 5a, and its 9-isoPr analogue, 12a. Treatment of 9a with excess NaBH(4) in AcOH gave (+/-)-coralydine (10b).
Assuntos
Antineoplásicos/síntese química , Isoquinolinas/síntese química , Lactamas/síntese química , Antineoplásicos/farmacologia , Indicadores e Reagentes , Compostos de LítioRESUMO
3 beta-Hydroxy-5 alpha-androstan-17-one was transformed into 17-oxa-5 alpha-androstan-3 beta-ol in five steps involving conversion of the 17-ketone via the corresponding lactol to its hypoiodite and thence a regioselective beta-scission under irradiation to give ring D seco iodoformate, from which the 17-oxasteroids were derived. Four bisheterosteroids 3,17-dioxa-5 alpha-androstane, 3-thia-17-oxa-5 alpha-androstane, 3-aza-17-oxa-5 alpha-androstane, and 3-selena-17-oxa-5 alpha-androstane) were synthesized from 17-oxa-5 alpha-androstan-3 beta-ol via 5, 8, 8, and 9 steps, respectively, involving a second regioselective beta-scission of an alkoxyl radical as the key step.
