From chiral bromo[13,14Cn]acetyl sultams to complex molecules singly/multiply labelled with isotopic carbon
From chiral bromo[13,14Cn]acetyl sultams to complex molecules singly/multiply labelled with isotopic carbon
复制标题
从手性溴[13,14Cn]乙酰磺内酰胺到同位素碳单/多重标记的复杂分子
DOI：
10.1002/jlcr.610
复制
发表时间：
2002
影响因子：
1.8
通讯作者：
R. Voges
中科院分区：
文献类型：
--
作者：
R. Voges
手性溴代[13，14 Cn]乙酰基磺内酰胺（+）-和（-）-[13，14 Cn]BABS 1a，1b已被证明是许多对映体纯的单标记和多标记结构单元的高效、通用和实用的配体。衍生自1a、1b的三氯钛烯醇化物与醛进行羟醛加成反应，提供具有优异的非对映选择性的易于纯化的结晶顺式-2-溴-3-羟基[13，14 Cn]羧酸衍生物。这些可用作例如单/多标记的α-取代的β-羟基酸、β-取代的/支链的α-羟基酸和α-未取代的β-羟基酸的起始材料。此外，1a，1b可以很容易地转化为（+）/（-）-[13，14 Cn]DPMGBS 6，（+）/（-）-[13，14 Cn]ITCABS 8和（+）/（-）-[13，14 Cn]PABS 10等离子体，这显著地扩大了容易获得的中间体的光谱。6提供e. p.标记α-氨基酸，8可用于制备e. p.标记α-氨基-β-羟基酸（苏氨酸型）。合成子10与醛反应生成手性E-构型的烯酰基磺酰胺11，其用作多种e. p.单/多标记的α，β-取代/支链的无环和环状羧酸衍生物的起始材料。最后，通过还原性裂解来自伯α，β-取代的酰基磺酰胺的助剂而产生的醛与Ph 3 P =COOR反应，得到γ，δ-取代的α，β-不饱和酯，其进而可以容易地转化为高度官能化的e. p.标记的中间体。该方法已被广泛用于合成广谱碳-14标记的药物，例如紫杉醇、缬沙坦、依维莫司、脂质X、NVP IMM 125、SDZ ISQ 844、SDZ PR 105和环孢菌素衍生物Valspodar、NVP IMM 125、NVP NIM 811。版权所有© 2002年约翰威利父子有限公司。
The chiral bromo[13,14Cn]acetyl sultams (+)- and (−)-[13,14Cn]BABS 1a, 1b have been demonstrated to be highly efficient, versatile and practical synthons to numerous enantiomerically pure singly and multiply labelled building blocks. The trichlorotitanium enolates derived from 1a, 1b undergo aldol addition reactions with aldehydes providing easily purified, crystalline syn-2-bromo-3-hydroxy [13,14Cn]carboxylic acid derivatives with excellent diastereo-selectivity. These can serve as starting materials for e.p. singly/multiply labelled α-substituted β-hydroxy acids, β-substituted/branched α-hydroxy acids and α-unsubstituted β-hydroxy acids. Furthermore, 1a, 1b can be easily converted to the (+)/(−)-[13,14Cn]DPMGBS 6, (+)/(−)-[13,14Cn]ITCABS 8 and (+)/(−)-[13,14Cn]PABS 10 synthons, which significantly enlarges the spectrum of readiliy accessible intermediates. 6 Provides e.p. labelled α-amino acids, 8 can be employed for the preparation of e.p. labelled α-amino-β-hydroxy acids (threonine type). Synthon 10 reacts with aldehydes to chiral E-configured enoyl sultams 11 which serve as starting materials for a broad variety of e.p. singly/multiply labelled α,β-substituted/branched, acyclic and cyclic carboxylic acid derivatives. Finally, aldehydes, generated by reductive cleavage of the auxiliary from the primary α,β-substituted acyl sultams, react with Ph3P=COOR to give γ,δ-substituted α,β,-unsaturated esters, which in turn can be readily converted to highly functionalized e.p. labelled intermediates. This methodology has been extensively exploited for the synthesis of a broad spectrum of carbon-14 labelled drug substances e.g. Taxol, Valsartan, Everolimus, Lipid X, NVP IMM125, SDZ ISQ844, SDZ PRI05 and the cyclosporin derivatives Valspodar, NVP IMM125, NVP NIM811. Copyright © 2002 John Wiley & Sons, Ltd.