TOTAL SYNTHESIS OF GROSSULARINES-1 AND-2
TOTAL SYNTHESIS OF GROSSULARINES-1 AND-2
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DOI：
10.1021/jo00123a028
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发表时间：
1995-09-08
影响因子：
3.6
通讯作者：
HIBINO, S
中科院分区：
文献类型：
--
作者：
CHOSHI, T;YAMADA, S;HIBINO, S
首次完成了罗汉果甜素-1（1a）和-2（1b）的全合成。3-碘吲哚-2-羧酸乙酯（6）与咪唑9 b发生交叉偶联反应，得到3-（5-咪唑基）吲哚-2-羧酸乙酯11b。水解11b的酯基，然后进行Curtius重排，得到2-异氰酸根合吲哚13 b。进行13 B的热电环化反应以提供所需的四环吡啶并[2，3-B]吲哚环体系14 B，将其转化为三氟甲磺酸酯15 B。三氟甲磺酸酯15 b、一氧化碳和对-（O-苯基）硼酸（17）的三组分交叉偶联反应，然后水解，以低收率得到了grossularine-2（1b）。此外，三氟甲磺酸酯15 b的钯催化羰基化得到N-脱保护的甲酯19 a或甲酯19 b，这取决于三乙胺的用量。化合物19 a用对-（O-）苯基锂或3-（N-TIPS）吲哚基锂处理，分别得到grossularine-2（1b）和grossularine-1（1a）（37%）。与此相反，当用相同的芳基锂试剂处理19 b时，分别产生了grossularine-2（1b）（51%）和grossularine-1（1a）（63%）。
The first total syntheses of grossularines-1 (1a) and -2 (1b) have been completed. The cross-coupling reaction between ethyl 3-iodoindole-2-carboxylate (6) and the directed metalation-derived imidazole 9b gave the ethyl 3-(5-imidazolyl)indole-2-carboxylate 11b. Hydrolysis of the ester group of 11b, followed by Curtius rearrangement, yielded the 2-isocyanatoindole 13b. The thermal electrocyclic reaction of 13b was carried out to provide the desired tetracyclic pyrido[2,3-b]indole ring system 14b, which was converted into the triflate 15b. The three-component cross-coupling reaction of the triflate 15b, carbon monoxide, and p-(OMOM)phenylboronic acid (17) followed by hydrolysis gave grossularine-2 (1b) in low yield. In addition, the palladium-catalyzed carbonylation of the triflate 15b afforded the N-deprotected methyl ester 19a or the methyl ester 19b depending on the amounts of triethylamine used. Compound 19a was treated with either p-(OMOM)phenyllithium or 3-(N-TIPS)indolyllithium to obtain grossularine-2 (1b) and grossularine-1 (1a) (37%), respectively. By contrast, when 19b was treated with the same aryllithium reagents, grossularine-2 (1b) (51%) and grossularine-1 (1a) (63%) were produced, respectively.