| Co-Investigator(Kenkyū-buntansha) |
NAKAI Tatuya Meiji College of Pharm. Fac. of Pharm. Sciences Assistant, 薬学部, 助手 (80217645)
SAITO Naoki Meiji College of Pharm. Fac. of Pharm. Sciences Assistant, 薬学部, 助手 (80142545)
NAKAHARA Shinsuke Meiji College of Pharm. Fac. of Pharm. Sciences Lecturer, 薬学部, 講師 (60180337)
KITAHARA Yoshiyasu Meiji College of Pharm. Fac. of Pharm. Sciences Lecturer, 薬学部, 講師 (70114460)
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| Research Abstract |
Recently several naturally occurring isoquinolinequinone antibiotics have been isolated from Actinomycetes and from marine organisms. The unique structure of this antibiotics, coupled with their great biological activities, offers a formidable challenge to the synthetic chemist. Our basic plan involves the use of the 2,5-piperazinediones to construct the basic skeleton of this target having highly alkylated piperazine ring. The purpose of this paper is outline the general approach and progress that we have made toward this challenging target. The results are summarized as followed:
1) We succeed in a 19-step total synthesis of (<plus-minus>)-saframycin B from (Z)-1-acetyl-3-arylidene-6-(arylmethyl)-2,5-piperazinedione. 2) Three minor components of safiamycin group antibiotics, saframycins F, G, H were isolated and their structure were determined by comparison with the spectral data of natural products and the intermediates of a total synthesis of saframycin B. 3) An efficient synthesis of 1-methyl-3-(2,4,5-trimethoxy-3-methylphenylmethyl)-2,5-piperazinedione, which is shown to be a useful intermediate for preparation of the 1,5-imino-3-benzazocine derivative (right half of safraniycins). 4) A mild and efficient method for the synthesis of 1,2,3,4-tetrahydioisoquinolines by a modified Pictet-Spengler reaction involving Lewis acid-mediated cyclization of the O, N-acetals. This reaction is demonstrated with a preparation of the basic skeleton of the left half of saframycins. 5) A synthetic strategy for the preparation of isoquinoline antibiotic, saframycin A is outlined. 6) 9-Methoxy-3,8,11-trimeth-oxy-4-oxo-1,2,3,4,5,6-hexahydro-1,5-imino-3-benzazocin-7,10-dione is oxidized to the corresponding 6-hydroxy compound with selenium oxide. This is a good way to make saframycins C and D from saframycin B. 7) Synthetic approach of renieramycin A and a revised structure for renieramycins are presente
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