(5S)-3-[(E)-9-iodo-8-nonenyl]-5-methyl-3-(phenylsulfanyl)dihydro-2(3H)-furanone -Drug Synthesis Database

【结构式】

【分子编号】20205

【品名】(5S)-3-[(E)-9-iodo-8-nonenyl]-5-methyl-3-(phenylsulfanyl)dihydro-2(3H)-furanone

【CA登记号】

【分子式】C₂₀H₂₇IO₂S

【分子量】458.40365

【元素组成】C 52.4% H 5.94% I 27.68% O 6.98% S 7%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XXIV)

2) The reduction of (XIV) with DIBAL followed by protection with methoxymethyl chloride (MOM-Cl) yields the methoxymethyl ether (XV), which by regioselective dihydroxylation with AD-mix-beta, followed by mesylation with mesyl chloride affords the dimesylate (XVI). A new regioselective dihydroxylation of (XVI) with AD-mix-beta gives the diol (XVII), which is cyclized by treatment first with p-toluenesulfonic acid and then by heating at 140 C in pyridine yielding the bis(tetrahydrofuran) derivative (XVIII). The deprotection of (XVIII) with boron trilfuoride.ethearate, followed by tosylation with tosyl chloride in pyridine affords the tosylate (XIX), which is cyclized to the epoxide (XX) by reaction with K2CO3 in methanol. The acetylation of the secondary alcohol of (XIX) with acetic anhydride in pyridine affords the acetate (XXI), which is condensed with trimethylsilylacetylene (XXII) by means of n-BuLi in THF giving the acetylenic alcohol (XXIII).

参考文献中间体

合成目标

【1】 Yazbak, A.; et al.; Total synthesis of uvaricin. J Org Chem 1998, 63, 17, 5863.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	20188	ethyl (2E,6E)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2,6-nonadienoate		C₂₆H₄₆O₄	详情	详情
(XV)	20190	(2E,6E)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2,6-nonadienyl methoxymethyl ether; (4S,5R)-4-decyl-5-[(3E,7E)-9-(methoxymethoxy)-3,7-nonadienyl]-2,2-dimethyl-1,3-dioxolane		C₂₆H₄₈O₄	详情	详情
(XVI)	20191	(4S,5R)-4-decyl-5-((3S,4S,7E)-9-(methoxymethoxy)-3,4-bis[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-7-nonenyl)-2,2-dimethyl-1,3-dioxolane; (E,6S,7S)-9-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]-6,7-bis[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-nonenyl methoxymethyl ether		C₃₂H₆₂O₆S₂	详情	详情
(XVII)	20192	(4S,5S,8R,9R)-4-[2-[(4R,5S)-5-decyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl]-2-methyl-5-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-methylene-3,11,13-trioxa-2lambda(6)-thia-1-tetradecene-8,9-diol		C₃₂H₆₄O₈S₂	详情	详情
(XVIII)	20193	1(S)-[5(R)-[5(R)-[1(R)-Hydroxy-2-(methoxymethoxy)ethyl]tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecan-1-ol		C₂₃H₄₄O₆	详情	详情
(XIX)	20194	1(S)-[5(R)-[5(R)-[1(R)-Hydroxy-2-(p-toluenesulfonyloxy)ethyl]tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecan-1-ol		C₂₈H₄₆O₇S	详情	详情
(XX)	20195	1(S)-[5(R)-[5(R)-(1(R),2-Epoxyethyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecan-1-ol		C₂₁H₃₈O₄	详情	详情
(XXI)	20196	Acetic acid 1(S)-[5(R)-[5(R)-(1(R),2-Epoxyethyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecyl ester		C₂₃H₄₀O₅	详情	详情
(XXII)	23897	ethynyl(trimethyl)silane；trimethylsilyl acetylene	1066-54-2	C₅H₁₀Si	详情	详情
(XXIII)	20198	Acetic acid 1(S)-[5(R)-[5(R)-(1(R)-hydoxy-3-butynyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]undecyl ester		C₂₅H₄₂O₅	详情	详情
(XXIV)	20205	(5S)-3-[(E)-9-iodo-8-nonenyl]-5-methyl-3-(phenylsulfanyl)dihydro-2(3H)-furanone		C₂₀H₂₇IO₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXIV)

4) The intermediate iodinated tetrahydrofuranone (XXIV) has been obtained as follows: The silylation of 8-nonyn-1-ol (XXVII) with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole in DMF gives the silyl ether (XXVIII), which is iodinated by means of tributyltin hydride, azobis(cyclohexanecarbonitrile) (ABCN) and iodine yielding the iodovinyl compound (XXIX). The deprotection of (XXIX) with tetrabutylammonium fluoride in THF, followed by tosylation with tosyl chloride in pyridine affords the tosylate (XXX), which by reaction with NaI in acetone affords 1,9-diiodo-1-nonene (XXXI). Finally, this compound is condensed with (5S)-methyl-3-(phenylsulfanyl)tetrahydrofuran-2-one (XXXII) by means of potassium bis(trimthylsilyl)amide in THF to afford the desired intermediate (XXIV).

参考文献中间体

合成目标

【1】 Yazbak, A.; et al.; Total synthesis of uvaricin. J Org Chem 1998, 63, 17, 5863.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXIV)	20205	(5S)-3-[(E)-9-iodo-8-nonenyl]-5-methyl-3-(phenylsulfanyl)dihydro-2(3H)-furanone	C₂₀H₂₇IO₂S	详情	详情
(XXVII)	20199	8-nonyn-1-ol	C₉H₁₆O	详情	详情
(XXVIII)	20200	tert-butyl(dimethyl)(8-nonynyloxy)silane; tert-butyl(dimethyl)silyl 8-nonynyl ether	C₁₅H₃₀OSi	详情	详情
(XXIX)	20201	tert-butyl[[(E)-9-iodo-8-nonenyl]oxy]dimethylsilane; tert-butyl(dimethyl)silyl (E)-9-iodo-8-nonenyl ether	C₁₅H₃₁IOSi	详情	详情
(XXX)	20202	(E)-9-iodo-8-nonenyl 4-methylbenzenesulfonate	C₁₆H₂₃IO₃S	详情	详情
(XXXI)	20203	(E)-1,9-diiodo-1-nonene	C₉H₁₆I₂	详情	详情
(XXXII)	20204	(5S)-5-methyl-3-(phenylsulfanyl)dihydro-2(3H)-furanone	C₁₁H₁₂O₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXIV)

3) The addition of the iodinated tetrahydofuranone (XXIV) to the triple bond of (XXIII) catalyzed by CuI and palladium tetrakis(triphenylphosphine) in triethylamine yields intermediate (XXV) with a double and a triple bonds that are hydrogenated with H2 over a rhodium triphenylphosphine complex in benzene/methanol affording the saturated tridecanol (XXVI). Finally, the double bond of the dihydrofuranone ring of uvaricin is formed by oxidation of the phenylsulfanyl group to the corresponding sulfonyl derivative with m-chloroperbenzoic acid in dichloromethane followed by elimination of benzenesulfonic acid by refluxing in toluene.

参考文献中间体

合成目标

【1】 Yazbak, A.; et al.; Total synthesis of uvaricin. J Org Chem 1998, 63, 17, 5863.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXIV)	20205	(5S)-3-[(E)-9-iodo-8-nonenyl]-5-methyl-3-(phenylsulfanyl)dihydro-2(3H)-furanone	C₂₀H₂₇IO₂S	详情	详情
(XXV)	20206	3-[13(R)-[5(R)-[5(R)-(1(S)-Acetoxyundecyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]-13-hydroxytrideca-8(E)-en-10-ynyl]-5(S)-methyl-3-(phenylsulfanyl)tetrahydrofuran-2-one	C₄₅H₆₈O₇S	详情	详情
(XXVI)	20207	3-[13(R)-[5(R)-[5(R)-(1(S)-Acetoxyundecyl)tetrahydrofuran-2(R)-yl]tetrahydrofuran-2(R)-yl]-13-hydroxytridecyl]-5(S)-methyl-3-(phenylsulfanyl)tetrahydrofuran-2-one	C₄₅H₇₄O₇S	详情	详情

Extended Information