BAL-8349, RO-0098349
Chemical Name: Cyclo[D-alanyl-L-tyrosyl-L-valyl-4(R)-hydroxy-L-prolyl-D-allothreonyl-L-threonyl-3(S)-hydroxy-L-prolyl-3(R)-hydroxy-L-glutaminyl-glycyl-D-allothreonyl-N-delta-(3-aminopropyl)-Ndelta-(L-ornithyl)-L-ornithyl-3(R)-hydroxyhexadecanoyl-D-allothreonyl] tris(trifluoroacetate)
CAS No. 351435-84-2 (free base), 351435-85-3 (stereoisomer, free base), 351499-37-1 (stereoisomer, free base)
项目整合开发状态: Preclinical
项目研究机构: Basilea Pharmaceutica (Proprietary), Roche (Originator)
合成路线:The natural macrocyclic depsipeptide RO-0093655 (IV) was subjected to reductive alkylation with N-Boc-aminoacetaldehyde (II),yielding the mono-protected diamino compound (V).Subsequent acylation of amine (V) with the ornithine derivative (III) provided the corresponding amide (VI).
合成路线:The title compound was obtained by acidic cleavage of the Boc protecting groups of (VI) in the presence of trifluoroacetic acid.
合成路线:The title compound was prepared by chemical modification of the natural macrocyclic depsipeptide RO-0093655 (I).Conjugate addition of acrylonitrile (II) to the side-chain amino group of (I) produced the aminopropionitrile derivative (III).Subsequent acylation of aminonitrile (III) with the di-Boc-protected L-ornithine (IV) gave amide (V).
合成路线:The Boc protecting groups of (V) were removed by treatment with trifluoroacetic acid yielding diamine (VI).Finally,the cyano group of (VI) was reduced by catalytic hydrogenation over Pd/C to afford the title compound.
📌 参考资料/链接：
参考文献标题:Novel cyclic cpds.
文献作者:Okada,T.; Shimma,N.; Murata,T.; Masubuchi,K.; Kohchi,M.(Basilea Pharmaceutica AG)
参考来源:EP 1254161; WO 0153322
📄 详细内容
合成路线:The natural macrocyclic depsipeptide RO-0093655 (IV) was subjected to reductive alkylation with N-Boc-aminoacetaldehyde (II),yielding the mono-protected diamino compound (V).Subsequent acylation of amine (V) with the ornithine derivative (III) provided the corresponding amide (VI).
合成路线:The title compound was obtained by acidic cleavage of the Boc protecting groups of (VI) in the presence of trifluoroacetic acid.
合成路线:The title compound was prepared by chemical modification of the natural macrocyclic depsipeptide RO-0093655 (I).Conjugate addition of acrylonitrile (II) to the side-chain amino group of (I) produced the aminopropionitrile derivative (III).Subsequent acylation of aminonitrile (III) with the di-Boc-protected L-ornithine (IV) gave amide (V).
合成路线:The Boc protecting groups of (V) were removed by treatment with trifluoroacetic acid yielding diamine (VI).Finally,the cyano group of (VI) was reduced by catalytic hydrogenation over Pd/C to afford the title compound.
参考文献标题:Nasally administrable cyclic peptide compsns.
文献作者:Shimma,N.; Kobayashi,K.; Horii,I.; Yanagawa,A.(Basilea Pharmaceutica AG)
参考来源:WO 0152894
合成路线:The requisite N-Boc protected tetraamino carboxylic acid (III) was prepared by reductive dialkylation of N-delta-Boc-L-ornithine (I) with N-Boc-aminoacetaldehyde (II) in the presence of sodium cyanoborohydride.
合成路线:The natural macrocyclic depsipeptide RO-0093655 (IV) was subjected to reductive alkylation with N-Boc-aminoacetaldehyde (II),yielding the mono-protected diamino compound (V).Subsequent acylation of amine (V) with the ornithine derivative (III) provided the corresponding amide (VI).
合成路线:The title compound was obtained by acidic cleavage of the Boc protecting groups of (VI) in the presence of trifluoroacetic acid.
合成路线:The title compound was prepared by chemical modification of the natural macrocyclic depsipeptide RO-0093655 (I).Conjugate addition of acrylonitrile (II) to the side-chain amino group of (I) produced the aminopropionitrile derivative (III).Subsequent acylation of aminonitrile (III) with the di-Boc-protected L-ornithine (IV) gave amide (V).
合成路线:The Boc protecting groups of (V) were removed by treatment with trifluoroacetic acid yielding diamine (VI).Finally,the cyano group of (VI) was reduced by catalytic hydrogenation over Pd/C to afford the title compound.
参考文献标题:Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitor.Part 2
文献作者:Masubuchi,K.; Okada,T.; Kohchi,M.; Murata,T.; Tsukazaki,M.; Kondoh,O.; Yamazaki,T.; Satoh,Y.; Ono,Y.; Tsukaguchi,T.; Kobayashi,K.; Ono,N.; Inoue,T.; Horii,I.; Shimma,N.
参考来源:Bioorg Med Chem Lett 2001,11(10),1273
合成路线:The natural macrocyclic depsipeptide RO-0093655 (IV) was subjected to reductive alkylation with N-Boc-aminoacetaldehyde (II),yielding the mono-protected diamino compound (V).Subsequent acylation of amine (V) with the ornithine derivative (III) provided the corresponding amide (VI).
合成路线:The title compound was obtained by acidic cleavage of the Boc protecting groups of (VI) in the presence of trifluoroacetic acid.
合成路线:The title compound was prepared by chemical modification of the natural macrocyclic depsipeptide RO-0093655 (I).Conjugate addition of acrylonitrile (II) to the side-chain amino group of (I) produced the aminopropionitrile derivative (III).Subsequent acylation of aminonitrile (III) with the di-Boc-protected L-ornithine (IV) gave amide (V).
合成路线:The Boc protecting groups of (V) were removed by treatment with trifluoroacetic acid yielding diamine (VI).Finally,the cyano group of (VI) was reduced by catalytic hydrogenation over Pd/C to afford the title compound.
参考文献标题:Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors
文献作者:Okada,T.; et al.
参考来源:223rd ACS Natl Meet (April 7 2002,Orlando) 2002,Abst MEDI 174