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).

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.

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).

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.

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.

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).

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.

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.

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).

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.

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.