TOTAL SYNTHESIS OF GROSSULARINES-1 AND-2

被引:89
作者
CHOSHI, T [1 ]
YAMADA, S [1 ]
SUGINO, E [1 ]
KUWADA, T [1 ]
HIBINO, S [1 ]
机构
[1] FUKUYAMA UNIV,FAC PHARM & PHARMACEUT SCI,FUKUYAMA,HIROSHIMA 72902,JAPAN
关键词
D O I
10.1021/jo00123a028
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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.
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页码:5899 / 5904
页数:6
相关论文
共 32 条
  • [1] A SHORT ENTRY INTO THE PYRIDO[2,3-B]INDOLE RING-SYSTEM - SYNTHESIS OF THE TETRACYCLIC SEGMENT OF THE MARINE ANTITUMOR AGENTS - GROSSULARINE-1 AND GROSSULARINE-2
    ACHAB, S
    GUYOT, M
    POTIER, P
    [J]. TETRAHEDRON LETTERS, 1993, 34 (13) : 2127 - 2130
  • [2] AN EXPEDITIOUS SYNTHESIS OF STRUCTURAL ANALOGS OF THE MARINE CYTOTOXIC AGENTS GROSSULARINES-1 AND GROSSULARINES-2
    ACHAB, S
    GUYOT, M
    POTIER, P
    [J]. TETRAHEDRON LETTERS, 1995, 36 (15) : 2615 - 2618
  • [3] PALLADIUM-CATALYZED CARBONYLATION OF ARYL TRIFLATES - SYNTHESIS OF ARENECARBOXYLIC ACID-DERIVATIVES FROM PHENOLS
    CACCHI, S
    CIATTINI, PG
    MORERA, E
    ORTAR, G
    [J]. TETRAHEDRON LETTERS, 1986, 27 (33) : 3931 - 3934
  • [4] CARPENTER AJ, 1983, J CHEM RES S, P196
  • [5] CARRE PD, 1986, ACTA CRYSTALLOGR C, V42, P483
  • [6] SYNTHESIS OF MUTAGENIC HETEROCYCLIC AMINES PHIP AND DMIP
    CHOSHI, T
    TONARI, A
    YOSHIOKA, H
    HARADA, K
    SUGINO, E
    HIBINO, S
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (27) : 7952 - 7954
  • [7] CHOSHI T, 1995, SYNLETT, V147
  • [8] SYNTHESIS OF 2-DIMETHYLAMINOIMIDAZOLE DERIVATIVES - A NEW ACCESS TO INDOLYL-IMIDAZOLE ALKALOIDS OF MARINE ORIGIN
    DALKAFOUKI, A
    ARDISSON, J
    KUNESCH, N
    LACOMBE, L
    POISSON, JE
    [J]. TETRAHEDRON LETTERS, 1991, 32 (39) : 5325 - 5328
  • [9] NEW SYNTHESIS OF PYRIDINE DERIVATIVES
    ELOY, F
    DERYCKER.A
    [J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 1970, 7 (05) : 1191 - &
  • [10] GENERAL METHOD FOR SYNTHESIS OF CONDENSED 2-PYRIDONES
    ELOY, F
    DERYCKER.A
    [J]. HELVETICA CHIMICA ACTA, 1970, 53 (03) : 645 - &