White James D, Hansen Joshua D
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, USA.
J Org Chem. 2005 Mar 18;70(6):1963-77. doi: 10.1021/jo0486387.
[reaction: see text] The Z and E nitrones 38 and 39 from condensation of aldehyde 20 with hydroxylamine 36 underwent intramolecular dipolar cycloaddition to give the substituted 1-aza-7-oxobicyclo[2.2.1] heptanes 40 and 41 in a ratio of 2:1, respectively. Reductive N-O bond cleavage of 40 followed by carbonylation gave cyclic urea 47 in which inversion of the secondary alcohol was effected via an oxidation-reduction sequence. After conversion of the p-bromobenzyl ether 50 to azide 54, activation of the cyclic urea as its O-methylisourea and reduction of the azide led to spontaneous cyclization to afford the tricyclic nucleus 59 of cylindrospermopsin. Global deprotection, including hydrolysis of the 2,4-dimethyoxypyrimidine appendage to a uracil, and then monosulfation of the resultant diol 60 afforded a substance identical with natural (-)-7-epicylindrospermopsin (1). The asymmetric synthesis of (-)-7-epicylindrospermopsin defines its absolute configuration as 7S,8R,10S,12S,13R,14S.
[反应：见正文]醛20与羟胺36缩合得到的Z型和E型硝酮38和39发生分子内偶极环加成反应，分别以2:1的比例得到取代的1-氮杂-7-氧代双环[2.2.1]庚烷40和41。40的N-O键还原裂解，随后进行羰基化反应，得到环状脲47，其中仲醇的构型翻转是通过氧化还原序列实现的。将对溴苄基醚50转化为叠氮化物54后，环状脲作为其O-甲基异脲活化，叠氮化物还原导致自发环化，得到柱孢藻毒素的三环核59。包括将2,4-二甲氧基嘧啶附属物水解为尿嘧啶在内的全面脱保护，然后对所得二醇60进行单硫酸化，得到一种与天然（-）-7-表柱孢藻毒素（1）相同的物质。（-）-7-表柱孢藻毒素的不对称合成确定其绝对构型为7S，8R，10S，12S，13R，14S。
