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trans-ISA-247, ISA-247, R-1524, ISAtx-247

1,4,7,10,13,16,19,22,25,28,31-十一aza环三三康坦,环肽衍生物 Chemical Name: Cyclo[L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-[3(R)-hydroxy-N,4(R)-dimethyl-L-2-amino-6(E),8-nonadienoyl]-L-(2-aminobutyryl)-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl]; Cyclo[[3(R)-hydroxy-4(R)-methyl-2(S)-(methylamino)-6(E),8-nonadienoyl]-L-(2-aminobutyryl)-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl]; 6-[3(R)-Hydroxy-4(R)-methyl-2(S)-(methylamino)-6(E),8-nonadienoic acid]cyclosporin A
CAS No. 515814-01-4, 121584-34-7 (cis-isomer), 222295-79-6 (labeled), 515814-00-3 (undefined isomer)
项目整合开发状态: Phase II
项目研究机构: Isotechnika (Originator), Roche (Licensee)
合成路线:Acylation of ciclosporin (I) with Ac2O and DMAP gives the acetoxy ciclosporin derivative (II),which is oxidized with O3,KMnO4,OsO4 or NaIO4 in acetonitrile to yield the carbaldehyde (III).The Wittig condensation of aldehyde (III) with either allyltriphenylphosphonium bromide (IV) by means of t-BuOK in THF or NaOH in toluene (1-3) or allyldiphenylphosphine oxide (V) by means of butyl lithium in THF (1,3) provides the (E)-diene derivative (VI),which is finally deacylated by means of K2CO3 in methanol (1-3).

合成路线:Bromination of the acetoxy ciclosporin (II) with NBS and AIBN in refluxing CCl4 yields the allyl bromide (VII),which is condensed with triphenylphosphine in toluene at 100 oC to afford the triphenylphosphonium bromide (VIII).Finally,bromide (VIII) is condensed with formaldehyde by means of NaOH followed by deacetylation with K2CO3 in MeOH.
📌 参考资料/链接:
参考文献标题:Novel cyclosporin analog formulations
文献作者:Yatscoff,R.W.; Foster,R.T.; Naicker,S.A.(Isotechnika Inc.)
参考来源:US 2003171264; WO 0332949

📄 详细内容


合成路线:Acylation of ciclosporin (I) with Ac2O and DMAP gives the acetoxy ciclosporin derivative (II),which is oxidized with O3,KMnO4,OsO4 or NaIO4 in acetonitrile to yield the carbaldehyde (III).The Wittig condensation of aldehyde (III) with either allyltriphenylphosphonium bromide (IV) by means of t-BuOK in THF or NaOH in toluene (1-3) or allyldiphenylphosphine oxide (V) by means of butyl lithium in THF (1,3) provides the (E)-diene derivative (VI),which is finally deacylated by means of K2CO3 in methanol (1-3).

合成路线:Bromination of the acetoxy ciclosporin (II) with NBS and AIBN in refluxing CCl4 yields the allyl bromide (VII),which is condensed with triphenylphosphine in toluene at 100 oC to afford the triphenylphosphonium bromide (VIII).Finally,bromide (VIII) is condensed with formaldehyde by means of NaOH followed by deacetylation with K2CO3 in MeOH.

合成路线: Condensation of aldehyde (III) with the silylated allylboronate (IX) in THF gives the silylated alcohol (X),which is submitted to a stereospecific elimination by means of concentrated H2SO4,and finally deacylated by means of K2CO3 in methanol.

参考文献标题:Synthesis of cyclosporin analogs
文献作者:Abel,M.; Yatscoff,R.W.; Foster,R.T.; Jayaraman,S.; Mair,H.-J.; Adam,J.-M.; Lohri,B.; Naicker,S.A.(F.Hoffmann-La Roche AG; Isotechnika Inc.)
参考来源:US 2003212249; WO 0333526


合成路线:Acylation of ciclosporin (I) with Ac2O and DMAP gives the acetoxy ciclosporin derivative (II),which is oxidized with O3,KMnO4,OsO4 or NaIO4 in acetonitrile to yield the carbaldehyde (III).The Wittig condensation of aldehyde (III) with either allyltriphenylphosphonium bromide (IV) by means of t-BuOK in THF or NaOH in toluene (1-3) or allyldiphenylphosphine oxide (V) by means of butyl lithium in THF (1,3) provides the (E)-diene derivative (VI),which is finally deacylated by means of K2CO3 in methanol (1-3).

合成路线:Bromination of the acetoxy ciclosporin (II) with NBS and AIBN in refluxing CCl4 yields the allyl bromide (VII),which is condensed with triphenylphosphine in toluene at 100 oC to afford the triphenylphosphonium bromide (VIII).Finally,bromide (VIII) is condensed with formaldehyde by means of NaOH followed by deacetylation with K2CO3 in MeOH.

合成路线: Condensation of aldehyde (III) with the silylated allylboronate (IX) in THF gives the silylated alcohol (X),which is submitted to a stereospecific elimination by means of concentrated H2SO4,and finally deacylated by means of K2CO3 in methanol.

参考文献标题:Cyclosporine analogue mixtures and their use as immunomodulating agents
文献作者:Yatscoff,R.W.; Foster,R.T.; Naicker,S.(Isotechnika Inc.)
参考来源:US 2003139326; WO 0333527


合成路线:Acylation of ciclosporin (I) with Ac2O and DMAP gives the acetoxy ciclosporin derivative (II),which is oxidized with O3,KMnO4,OsO4 or NaIO4 in acetonitrile to yield the carbaldehyde (III).The Wittig condensation of aldehyde (III) with either allyltriphenylphosphonium bromide (IV) by means of t-BuOK in THF or NaOH in toluene (1-3) or allyldiphenylphosphine oxide (V) by means of butyl lithium in THF (1,3) provides the (E)-diene derivative (VI),which is finally deacylated by means of K2CO3 in methanol (1-3).

合成路线:Bromination of the acetoxy ciclosporin (II) with NBS and AIBN in refluxing CCl4 yields the allyl bromide (VII),which is condensed with triphenylphosphine in toluene at 100 oC to afford the triphenylphosphonium bromide (VIII).Finally,bromide (VIII) is condensed with formaldehyde by means of NaOH followed by deacetylation with K2CO3 in MeOH.

合成路线: Condensation of aldehyde (III) with the silylated allylboronate (IX) in THF gives the silylated alcohol (X),which is submitted to a stereospecific elimination by means of concentrated H2SO4,and finally deacylated by means of K2CO3 in methanol.
参考文献标题:ISA-247
文献作者:McIntyre,J.A.; Castar,J.
参考来源:Drugs Fut 2004,29(7),680


产品链接: CAS No. 515814-01-4››

产品链接: CAS No.121584-34-7››