2-[(1R,3S,4R)-3-(acetyloxy)-4-(benzyloxy)-1-methyl-5-hexenyl]-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-pyraniumolate -Drug Synthesis Database

【结构式】

【分子编号】55250

【品名】2-[(1R,3S,4R)-3-(acetyloxy)-4-(benzyloxy)-1-methyl-5-hexenyl]-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-pyraniumolate

【CA登记号】

【分子式】C₂₈H₄₀O₆Si

【分子量】500.7075

【元素组成】C 67.17% H 8.05% O 19.17% Si 5.61%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XV)

Treatment of pyranone (XIV) with DBU in boiling acetonitrile generated the pyrilium intermediate (XV) which underwent intramolecular cycloaddition to the desired endo cycloadduct (XVI). Catalytic double bond hydrogenation of enone (XVI) provided the saturated ketone (XVII). Wittig reaction of (XVII) with methylene triphenylphosphorane, followed by reacetylation with acetyl chloride furnished the exocyclic methylene derivative (XVIII). Allylic oxidation of (XVIII) by means of SeO2 and t-BuOOH, and further MnO2 oxidation of the resultant alcohol led to the methylene ketone (XIX). This was then subjected to conjugate addition of vinyl cuprate to provide ketone (XX). Diastereoselective addition of the lithium acetylide (XXI) to ketone (XX) followed by quenching with N-methyl-N-(trimethylsilyl)trifluoroacetamide furnished the silyl ether (XXII) along with some unsilylated carbinol, which was converted to (XXII) by independent silylation with chlorotrimethylsilane and imidazole. The tricyclic system (XXIII) was then obtained by zirconocene-mediated cyclization of (XXII), followed by selective acetate hydrolysis with 90 % AcOH.

参考文献中间体

合成目标

【1】 Boger, D.L.; Searcey, M.; The first synthesis of a daphnane diterpene: The enantiocontrolled total synthesis of (+)-resiniferatoxin. Chemtracts - Org Chem 1998, 11, 9, 647.
【2】 Wender, P.A.; et al.; The first synthesis of a daphnane diterpene: The enantiocontrolled total synthesis of resiniferatoxin. J Am Chem Soc 1997, 119, 52, 12976.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIV)	55249	6-[(1R,3S,4R)-3-(acetyloxy)-4-(benzyloxy)-1-methyl-5-hexenyl]-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-oxo-5,6-dihydro-2H-pyran-2-yl acetate	C₃₀H₄₄O₈Si	详情	详情
(XV)	55250	2-[(1R,3S,4R)-3-(acetyloxy)-4-(benzyloxy)-1-methyl-5-hexenyl]-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-pyraniumolate	C₂₈H₄₀O₆Si	详情	详情
(XVI)	55251	(1R,2R,4S,5R,6S,8S)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-9-en-4-yl acetate	C₂₈H₄₀O₆Si	详情	详情
(XVII)	55252	(1R,2R,4S,5R,6S,8R)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate	C₂₈H₄₂O₆Si	详情	详情
(XVIII)	55253	(1R,2R,4S,5R,6S,8R)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-methylene-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate	C₂₉H₄₄O₅Si	详情	详情
(XIX)	55254	(1R,2R,4S,5R,6S,8S)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-methylene-10-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate	C₂₉H₄₂O₆Si	详情	详情
(XX)	55255	(1R,2R,4S,5R,6S,8S,11S)-11-allyl-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-10-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate	C₃₁H₄₆O₆Si	详情	详情
(XXI)	52731	(2-phenylethynyl)lithium	C₈H₅Li	详情	详情
(XXII)	55256	(1R,2R,4S,5R,6S,8S,10R,11S)-11-allyl-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-10-(2-phenylethynyl)-10-[(trimethylsilyl)oxy]-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate	C₄₂H₆₀O₆Si₂	详情	详情
(XXIII)	55257	(1R,2S,4S,6R,8S,10S,11R,12S,14R)-11-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,14-dimethyl-5-[(Z)-phenylmethylidene]-6-[(trimethylsilyl)oxy]-15-oxatetracyclo[6.6.1.0~1,10~.0~2,6~]pentadecan-12-ol	C₄₀H₆₀O₅Si₂	详情	详情

Extended Information