tributyl[(E,3S,5R)-5-(1,3-dithian-2-yl)-3-methyl-1-hexenyl]stannane -Drug Synthesis Database

【结构式】

【分子编号】14981

【品名】tributyl[(E,3S,5R)-5-(1,3-dithian-2-yl)-3-methyl-1-hexenyl]stannane

【CA登记号】

【分子式】C₂₃H₄₆S₂Sn

【分子量】505.46024

【元素组成】C 54.65% H 9.17% S 12.69% Sn 23.49%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XI)

A partial synthesis of rapamycin has been reported: The reaction of 1-(trimethylsilyl)-1,3-pentadiyne (I) with a stannyl cuprate gives a mixture of (E)- and (Z)-stannyl derivatives (II) and (III) [the ratio (II)/(III) depends on the stannyl cuprate used]. Both compounds, after chromatographic separation, are condensed with the chiral aldehyde (IV) by means of butyllithium to afford the alcohols (V) and (VI), respectively. By chromatographic separation of the corresponding (S)-isomers, these are methylated and deprotected with methyl iodide and KOH, yielding the (E)- and (Z)-isomeric terminal acetylenes (VII) and (VIII). The reaction of either (VII) or (VIII) with tributylstannyl hydride and AIBN in refluxing toluene gives in both cases the (E,E)-dienylstannane (IX), which by reaction with I2 in dichloromethane affords the (E,E)-dienyl iodide (X). Finally, this compound is condensed with the vinyl iodide (XI) (see later) by means of PdCl2 in DMF to yield (XII), the protected C(10)-C(26) fragment of rapamycin [the C(20)-C(35)-C(1)-O(36) fragment based on the IUPAC nomenclature recommendations].

参考文献中间体

合成目标

【1】 Maleczka, R.E.; Condon, S.M.; Leazer, J.L.; McCauley, J.A.; Smith, A.B.; Leahy, J.W.; Rapamycin synthetic studies. 2. Elaboration of the C(10)-C(26) perimeter. Tetrahedron Lett 1994, 35, 28, 4911.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	14971	trimethyl(1,3-pentadiynyl)silane	C₈H₁₂Si	详情	详情
(II)	14972	trimethyl[(E)-4-(tributylstannyl)-3-penten-1-ynyl]silane	C₂₀H₄₀SiSn	详情	详情
(III)	14973	trimethyl[(Z)-4-(tributylstannyl)-3-penten-1-ynyl]silane	C₂₀H₄₀SiSn	详情	详情
(IV)	14974	2-[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]acetaldehyde	C₁₂H₂₀O₄	详情	详情
(V)	14975	(E)-3-methyl-6-(trimethylsilyl)-1-[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]-3-hexen-5-yn-2-ol	C₂₀H₃₄O₄Si	详情	详情
(VI)	14976	(Z)-3-methyl-6-(trimethylsilyl)-1-[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]-3-hexen-5-yn-2-ol	C₂₀H₃₄O₄Si	详情	详情
(VII)	14977	methyl (1S,2E)-2-methyl-1-[[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]methyl]-2-penten-4-ynyl ether; (2R,3R,7S,10R)-7-[(2S,3E)-2-methoxy-3-methyl-3-hexen-5-ynyl]-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]decane	C₁₈H₂₈O₄	详情	详情
(VIII)	63930	(2R,3R,7S,10R)-7-[(2S,3Z)-2-methoxy-3-methyl-3-hexen-5-ynyl]-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]decane; methyl (1S,2Z)-2-methyl-1-{[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]methyl}-2-penten-4-ynyl ether	C₁₈H₂₈O₄	详情	详情
(IX)	14979	tributyl[(1E,3E,5S)-5-methoxy-4-methyl-6-[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]-1,3-hexadienyl]stannane	C₃₀H₅₆O₄Sn	详情	详情
(X)	14980	(1S,2E,4E)-5-iodo-2-methyl-1-[[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]methyl]-2,4-pentadienyl methyl ether; (2R,3R,7S,10R)-7-[(2S,3E,5E)-6-iodo-2-methoxy-3-methyl-3,5-hexadienyl]-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]decane	C₁₈H₂₉IO₄	详情	详情
(XI)	14981	tributyl[(E,3S,5R)-5-(1,3-dithian-2-yl)-3-methyl-1-hexenyl]stannane	C₂₃H₄₆S₂Sn	详情	详情
(XII)	14982	(2R,3R,7S,10R)-7-[(2S,3E,5E,7E,9S,11R)-11-(1,3-dithian-2-yl)-2-methoxy-3,9-dimethyl-3,5,7-dodecatrienyl]-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]decane; (1S,2E,4E,6E,8S,10R)-10-(1,3-dithian-2-yl)-2,8-dimethyl-1-[[(2R,3R,7S,10R)-2,3,10-trimethyl-1,4,6-trioxaspiro[4.5]dec-7-yl]methyl]-2,4,6-undecatrienyl methyl ether	C₂₉H₄₈O₄S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

The vinyl stannane fragment (XI) of the preceding synthesis (scheme 1756502a) is obtained as follows: Treatment of the meso-2,3-dimethylglutaric acid dimethyl ester (XIII) with alpha-chymotrypsin followed by reduction with borane.dimethylsulfide gives the chiral hydroxy ester (XIV), which is protected with BPSCl and the ester group reduced with DIBAL to afford the partially protected diol (XV). The oxidation of (XV) with oxalyl chloride and protection of the resulting aldehyde with propane-1,3-dithiol give the dithiane (XVI), which is deprotected with TBAF and oxidized with oxalyl chloride to yield the aldehyde (XVII). The olefination of (XVII) with methyl iodide and CrCl2 affords the trans-vinyl iodide (XVIII), which is finally treated with butyllithium and tributylstannyl bromide in ethyl ether to give the vinyl stannane fragment (XI).

参考文献中间体

合成目标

【1】 Maleczka, R.E.; Condon, S.M.; Leazer, J.L.; McCauley, J.A.; Smith, A.B.; Leahy, J.W.; Rapamycin synthetic studies. 2. Elaboration of the C(10)-C(26) perimeter. Tetrahedron Lett 1994, 35, 28, 4911.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	14981	tributyl[(E,3S,5R)-5-(1,3-dithian-2-yl)-3-methyl-1-hexenyl]stannane	C₂₃H₄₆S₂Sn	详情	详情
(XIII)	14983	dimethyl (2R,4S)-2,4-dimethylpentanedioate	C₉H₁₆O₄	详情	详情
(XIV)	14984	methyl (2R,4S)-5-hydroxy-2,4-dimethylpentanoate	C₈H₁₆O₃	详情	详情
(XV)	14985	(2R,4S)-5-[[tert-butyl(diphenyl)silyl]oxy]-2,4-dimethyl-1-pentanol	C₂₃H₃₄O₂Si	详情	详情
(XVI)	14986	tert-butyl(diphenyl)silyl (2S,4R)-4-(1,3-dithian-2-yl)-2-methylpentyl ether; tert-butyl[[(2S,4R)-4-(1,3-dithian-2-yl)-2-methylpentyl]oxy]diphenylsilane	C₂₆H₃₈OS₂Si	详情	详情
(XVII)	14987	(3S,5R)-5-(1,3-dithian-2-yl)-3-methylhexanal	C₁₁H₂₀OS₂	详情	详情
(XVIII)	14988	2-[(1R,3S,4E)-5-iodo-1,3-dimethyl-4-pentenyl]-1,3-dithiane	C₁₁H₁₉IS₂	详情	详情

Extended Information