NKS-01

(8R,9S,10R,13S)-14-羟基-10,13-二甲基-2,7,8,9,11,12,15,16-八氢-1H-环戊二烯并[a]菲-3,6,17-三酮Chemical Name: 14alpha-Hydroxy-4-androstene-3,6,17-trione
CAS No. 120051-39-0
项目整合开发状态: Phase II
项目研究机构: Nippon Kayaku (Originator), Snow Brand (Originator)
合成路线:NKS-01 can be obtained by four similar ways:1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II),which is then oxidized,either photochemically with oxygen in CHCl3 under sunlight ,with MgO2 at room temperature (2) or with CrO3/H2SO4.2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III),which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl).Finally,(IV) is oxidized with Jones' reagent (CrO3/H2SO4).3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid.4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium,such as Myrothecium sp.NK-928521 or natural or artificial mutants,gives (II),which is then oxidized with activated MgO2 in CHCl3 at room temperature.
📌 参考资料/链接:
参考文献标题:Novel androst-4-ene-3,17-dione derivs.and process for their preparation
文献作者:Yoshihama,M.; Tamura,K.; Miyata,N.; Nakayama,S.; Nakakoshi,M.(Snow Brand Milk Products Co.,Ltd.)
参考来源:JP 1988192794; JP 1988192795; JP 1988192796; JP 1988192797; US 4975368; WO 8805781

📄 详细内容


合成路线:NKS-01 can be obtained by four similar ways:1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II),which is then oxidized,either photochemically with oxygen in CHCl3 under sunlight ,with MgO2 at room temperature (2) or with CrO3/H2SO4.2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III),which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl).Finally,(IV) is oxidized with Jones' reagent (CrO3/H2SO4).3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid.4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium,such as Myrothecium sp.NK-928521 or natural or artificial mutants,gives (II),which is then oxidized with activated MgO2 in CHCl3 at room temperature.

参考文献标题:Process for preparing 14alpha-hydroxy-4-androstene-3,6,17-trione
文献作者:Nakakoshi,M.; Tamura,K.; Yoshihama,M.; Miyata,N.(Snow Brand Milk Products Co.,Ltd.)
参考来源:EP 0382162


合成路线:NKS-01 can be obtained by four similar ways:1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II),which is then oxidized,either photochemically with oxygen in CHCl3 under sunlight ,with MgO2 at room temperature (2) or with CrO3/H2SO4.2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III),which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl).Finally,(IV) is oxidized with Jones' reagent (CrO3/H2SO4).3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid.4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium,such as Myrothecium sp.NK-928521 or natural or artificial mutants,gives (II),which is then oxidized with activated MgO2 in CHCl3 at room temperature.

参考文献标题:Process for the preparation of 14alpha-hydroxy-4-androsten-3,6,17-trione
文献作者:Seya,M.; Nakamura,H.; Nakakoshi,M.(Snow Brand Milk Products Co.,Ltd.)
参考来源:JP 1991068596


合成路线:NKS-01 can be obtained by four similar ways:1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II),which is then oxidized,either photochemically with oxygen in CHCl3 under sunlight ,with MgO2 at room temperature (2) or with CrO3/H2SO4.2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III),which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl).Finally,(IV) is oxidized with Jones' reagent (CrO3/H2SO4).3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid.4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium,such as Myrothecium sp.NK-928521 or natural or artificial mutants,gives (II),which is then oxidized with activated MgO2 in CHCl3 at room temperature.

参考文献标题:Process for production of 6beta,14alpha-dihydroxy-4-androstene-3,17-dione
文献作者:Yoshioka,H.; Asada,H.; Fujita,S.(Nippon Kayaku Co.,Ltd.)
参考来源:EP 0599658


合成路线:NKS-01 can be obtained by four similar ways:1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II),which is then oxidized,either photochemically with oxygen in CHCl3 under sunlight ,with MgO2 at room temperature (2) or with CrO3/H2SO4.2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III),which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl).Finally,(IV) is oxidized with Jones' reagent (CrO3/H2SO4).3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid.4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium,such as Myrothecium sp.NK-928521 or natural or artificial mutants,gives (II),which is then oxidized with activated MgO2 in CHCl3 at room temperature.

参考文献标题:Microbial production of two new dihydroxylated androstenedione derivatives by Acremonium strictum
文献作者:Yoshihama,M.; Nakakoshi,M.; Tamura,K.; Miyata,N.; Kawanishi,G.
参考来源:J Ferment Bioeng 1989,67(4),238-43


合成路线:NKS-01 can be obtained by four similar ways:1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II),which is then oxidized,either photochemically with oxygen in CHCl3 under sunlight ,with MgO2 at room temperature (2) or with CrO3/H2SO4.2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III),which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl).Finally,(IV) is oxidized with Jones' reagent (CrO3/H2SO4).3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid.4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium,such as Myrothecium sp.NK-928521 or natural or artificial mutants,gives (II),which is then oxidized with activated MgO2 in CHCl3 at room temperature.

参考文献标题:NKS-01
文献作者:Graul,A.; Castar,J.
参考来源:Drugs Fut 1996,21(10),1028


合成路线:NKS-01 can be obtained by four similar ways:1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II),which is then oxidized,either photochemically with oxygen in CHCl3 under sunlight ,with MgO2 at room temperature (2) or with CrO3/H2SO4.2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III),which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl).Finally,(IV) is oxidized with Jones' reagent (CrO3/H2SO4).3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid.4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium,such as Myrothecium sp.NK-928521 or natural or artificial mutants,gives (II),which is then oxidized with activated MgO2 in CHCl3 at room temperature.
参考文献标题:New manufacturing method for 14alpha-hydroxy-4-androsten-3,6,17-trione
文献作者:Nakakoshi,M.; Yoshihama,M.; Nakamura,H.; et al.(Snow Brand Milk Products Co.,Ltd.)
参考来源:JP 9307687


产品链接: CAS No. 120051-39-0››