EFFICIENT SYNTHESIS OF DL-MALYNGOLIDE
EFFICIENT SYNTHESIS OF DL-MALYNGOLIDE
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DL-马林内酯的高效合成
DOI：
10.1021/jo00143a039
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Y. Moon
中科院分区：
文献类型：
--
作者：
S. H. Kim;C. Hong;Y. Moon
最近报道了从海洋蓝绿色细菌大鞘丝藻中分离得到的一种抗生素--马林高内酯的分离和结构测定。最近关于马林高利特合成的报道促使我们公开了我们的有效的五步合成，与以前的合成相比，该合成是用完全不同的方法（方案I）实现的。2-（甲氧羰基）环戊酮的钾盐与正壬基溴在二甲基亚砜中室温反应6 h，得到烷基化酮酯3，沿着少量副产物，推测为O-烷基化p r o d ~ ct。在不分离副产物的情况下，将混合物在室温下用间氯过氧苯甲酸和碳酸氢钠在氯仿中进行BaeyerVilliger氧化条件48 h，经硅胶柱色谱分离后，以85%的总收率从2得到β-内酯4。4在-78 ℃下用1.1当量二异丙基氨基锂处理，并在-45 ℃下用5当量碘甲烷和1.2当量六甲基磷酰胺甲基化，得到91%的所需甲基内酯5。将5用碘化锂在吡啶中回流水解8小时，得到酸6.96，将其转化为与氯甲酸乙酯的混合酸酐，在0 ℃下，用乙醚中的三乙胺还原，然后用乙醚中的硼氢化锌还原，得到70：30的马林高利特及其C-2差向异构体的混合物，通过硅胶柱色谱分离后，产率为80%。
Recently the isolation and structure determination of malyngolide, an antibiotic from the marine blue-green alga Lyngbya majuscula Gomont, was reported.' Recent reports on the synthesis of malyngolide prompt us to disclose our efficient five-step synthesis which has been achieved with an entirely different approach (Scheme I), compared to previous s y n t h e s e ~ . ~ , ~ Reaction of the potassium salt of 2-(carbomethoxy)cy~lopentanone~ with n-nonyl bromide in dimethyl sulfoxide at room temperature for 6 h provided the alkylated keto ester 3 along with a small amount of a byproduct, presumably O-alkylated p r o d ~ c t . ~ ~ ~ Without separation of the byproduct, the mixture was subjected to BaeyerVilliger oxidation conditions with m-chloroperoxybenzoic acid and sodium bicarbonate in chloroform a t room temperature for 48 h to afford &lactone 4 in an 85% overall yield from 2 after separation by silica gel column chromatography. 4 was treated with 1.1 equiv of lithium diisopropylamide a t -78 OC and methylated with 5 equiv of methyl iodide and 1.2 equiv of hexamethylphosphoramide a t -45 "C to afford the desired methyl lactone 5 in 91% Hydrolysis of 5 with lithium iodide in pyridine a t reflux for 8 h provided the acid 6.9 6 was converted to the mixed anhydride with ethyl chloroformate and triethylamine in ether at 0 OC, followed by reduction with zinc borohydride in ether to afford a 70:30 mixture of malyngolide and its C-2 epimer in 80% yield after separation by silica gel column chromatography.l0J1 The C-2