Anticoagulant peptide alcohols

Claim 1

A process for preparing a peptide alcohol derivative of the formula X-A₁-A₂-A₃-A₄-A₅-A₆-A₇-A₈-A₉-A₁₀-ol wherein X      is a hydrogen, one or two alkyl groups of from 1 to 6 carbon atoms, or one or two acyl groups of from 2 to 10 carbon atoms; A₁      is a bond or is a peptide fragment containing from one to eleven residues of any amino acid; A₂      is Phe, SubPhe, β-(2- and 3-thienyl)alanine, β-(2-­and 3-furanyl)alanine, β-(2-, 3-, and 4-pyridyl) alanine, β-(benzothienyl-2- and 3-yl)alanine, β-(1-­and 2-naphthyl)alanine, Tyr, or Trp; A₃      is Glu or Asp; A₄      is any amino acid; A₅      is Ile, Val, Leu, Nle, or Phe; A₆      is Pro, Hyp, 3,4-dehydroPro, thiazolidine-4-car­boxylate, Sar, NMePgl, or D-Ala; A₇      is any amino acid; A₈      is any amino acid; A₉      is a lipophilic amino acid selected from Tyr, Trp, Phe, Leu, Nle, Ile, Val, Cha and Pro or is a dipep­tide containing at least one of these lipophilic amino acids; A₁₀-ol      is a reduced peptide fragment containing from zero to five residues of any amino acid wherein the carbon terminal amino acid is reduced to its alco­hol derivative which comprises (a) binding a suitably protected amino acid corresponding to the A₉ amino acid to an activated resin support (b) subsequently binding the other alpha amino protected amino acids in order from the carboxy terminus to the amino terminus, A₈ through A₁, to the amino terminus of the growing peptidic chain which has meanwhile been exposed by removing its amino protecting group; and (c) finally treating the resin bound peptide with about 2 equivalents of the carboxy terminal amino alcohol corresponding to A₁₀-ol and about 1 equivalent of acetic acid in dichloromethane to release the peptide from the resin and concomitantly bind the carboxy terminal peptide alcohol to the peptide thus resulting in the desired peptide alcohol derivative.