SYNTHETIC STUDIES ON 2R,4',8'R-ALPHA-TOCOPHEROL - APPROACH UTILIZING SIDE-CHAIN SYNTHONS OF MICROBIOLOGICAL ORIGIN
SYNTHETIC STUDIES ON 2R,4',8'R-ALPHA-TOCOPHEROL - APPROACH UTILIZING SIDE-CHAIN SYNTHONS OF MICROBIOLOGICAL ORIGIN
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DOI：
10.1021/jo00884a002
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发表时间：
1976-01-01
影响因子：
3.6
通讯作者：
SAUCY, G
中科院分区：
文献类型：
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作者：
COHEN, N;EICHEL, WF;SAUCY, G
（2 R，4 ″ R，8 ″ R）-α-环己基-1，3-二氢-2，4-二氧杂环己基-1，3-二氧杂环己基-1，4-二氧杂环己基-1，3-二氢-2，4-二氧杂环己基-1本发明描述了生育酚乙酸酯（1，R = Ac），其中从（S）-（+）-3-羟基-2-甲基丙酸（6）开始制备关键的光学活性侧链双链体，所述（S）-（+）-3-羟基-2-甲基丙酸（6）容易通过异丁酸的细菌氧化获得。在最快速的方法中，将（S）-（+）-3-叔丁氧基-2-甲基-1-丙醇对甲苯磺酸盐（13，由6分3步制备）与（R）-3，7-二甲基-1-辛基溴化镁[33，衍生自（R）-（+）-胡薄荷酮]偶联，得到（2 R，6 R）-（+）-1-叔丁氧基-2，6，10-三甲基十一烷。然后将衍生的14-C格氏试剂与（S）-（+）-6-苄氧基-2，5，7，8-四甲基苯并二氢吡喃-2-乙醇对甲苯磺酸酯偶联，得到（2 R，4 ″ R，8 ″ R）-α-生育酚苄基醚和随后的1. 10-C介子（即，33)也可以由13通过（R）-（+）-3，7-二甲基辛酸制备，提供了一种方法，其中两个手性中心以及生育酚侧链的8个C均衍生自酸6。
A synthesis of (2R,4''R,8''R)-.alpha.-tocopheryl acetate (1, R = Ac) is described in which key, optically active side chain synthons are produced starting from (S)-(+)-3-hydroxy-2-methylpropanoic acid (6), readily available via the bacterial oxidation of isobutyric acid. In the most expeditious approach, (S)-(+)-3-tert-butoxy-2-methyl-1-propanol p-toluenesulfonate (13, produced in 3 steps from 6) is coupled with (R)-3,7-dimethyl-1-octylmagnesium bromide [33, derived from (R)-(+)-pulegone] giving (2R,6R)-(+)-1-tert-butoxy-2,6,10-trimethylundecane. The derived 14-C Grignard reagent is then coupled with (S)-(+)-6-benzyloxy-2,5,7,8-tetramethylchroman-2-ethanol p-toluenesulfonate giving (2R,4''R,8''R)-.alpha.-tocopheryl benzyl ether and subsequently 1. The 10-C synthons (i.e., 33) could also be prepared from 13 via (R)-(+)-3,7-dimethyloctanoic acid providing an approach in which both chiral centers as well as 8 C of the tocopherol side chain are derived from the acid 6.