Solid phase peptide synthesis of peptide alcohols

process for producing the following depsipeptide of formula (VII):

• wherein,
• the fragment A represents the amine-Cα(residue)- of an amino acid chosen in the group of natural or unnatural amino acids, n is an integer from 1 to 10;
• each R4 is independently selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C10 alkynyl group, a (C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a (C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, and a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, said groups being non substituted or substituted by 1 to 10 fluorine atoms, 1 to 5 —NRR′, 1 to 5 SH, 1 to 5OR, 1 to 5 COR, 1 to 5 COOR, 1 to 5 CONRR′, 1 to 5 NHCONH2, and/or 1 to 5 NHC(NH)NH2 moieties wherein R and R′ are independently from one another selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C10 alkynyl group, a (C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a (C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, and a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group;
• m is an integer from 1 to 100, wherein when m is greater than 1, the bracketed amino acid residue is the same or different;
• each R5 and R6 is independently selected from the group consisting of a hydrogen atom, a fluorine atom, a C1-C20 alkyl group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a (C4-C12) monocyclic or polycyclic hydrocarbonated group, a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic hydrocarbonated group, a —(C1-C10 alkyl)-S-(C1-C10 alkyl) group, a —(C1-C10 alkyl)-indol-2-yl group, and a -(C1-C10 alkyl)-imidazolyl group, said groups being non substituted or substituted by 1 to 10 fluorine atoms, 1 to 5 —NRR′, 1 to 5 SH, 1 to 5 OR, 1 to 5 COR, 1 to 5 COOR, 1 to 5 CONRR′, 1 to 5 NHCONH2, and/or 1 to 5 NHC(NH)NH2 moieties wherein R and R′ are independently selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C10 alkynyl group, a (C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a (C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, and a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, wherein the NH2, NH, COOH, SH and OH functions of these groups are optionally protected by one or several identical or different O-protecting and/or N-protecting and/or S-protecting groups or atoms;
• each R7 is independently selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6alkynyl group, a (C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a —(C1C10 alkyl)-(C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a (C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, and a CO—R group, wherein R represents a hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C10 alkynyl group, a (C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a —(C1-C10 alkyl)-(C4C12) monocyclic or polycyclic saturated hydrocarbonated group, a (C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, or a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group;
• R7 and R5, and/or R7 and R6 can form together with the atoms which carry them a monocyclic or polycyclic moiety wherein each ring is a 3- to 10-membered hydrocarbonated ring, saturated or unsaturated, the number of rings being comprised between 1 and 5, non-substituted or substituted by 1 to 10 fluorine atoms, 1 to 5 —NRR′, 1 to 5 SH, 1 to 5 OR, 1 to 5COR, 1 to 5 COOR, 1 to 5 CONRR′, 1 to 5 NHCONH2, and/or 1 to 5 NHC(NH)NH2 moieties wherein R and R′ are independently selected from the group consisting of a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C10 alkynyl group, a (C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic saturated hydrocarbonated group, a (C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, and a —(C1-C10 alkyl)-(C4-C12) monocyclic or polycyclic unsaturated hydrocarbonated group, wherein the NH2, NH, COOH, SH and OH functions of these groups are optionally protected by one or several identical or different O-protecting and/or N-protecting and/or S-protecting groups or atoms;
• P2 represents a hydrogen atom or an N-protecting group;
• and
• the α-carbon of each bracketed amino acid residue, marked 2, can independently have an R or S configuration if said α-carbon is an asymmetrical carbon,
• the process comprises:
• a) providing a solid phase amino alcohol of formula (I):
• wherein P1 represents an O-protecting group and ▭ represents a solid support appropriate for peptide synthesis;
• b) removing the O-protecting group P1 from the solid phase amino alcohol of formula (I);
• c) coupling a conveniently protected amino acid of formula (VI):
• d) removing the N-protecting group P2;
• e) repeating steps c) and d) 0 to 99 times;
• f) removing the solid support by acidic cleavage to yield the depsipeptide of formula (VII).