KR860008209A - Method of preparing cyclosporin - Google Patents

Abstract

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Description

Method of preparing cyclosporin

Since this is an open matter, no full text was included.

Claims (3)

The amino acid residue at position 8 is a (D) -acyloxy-α-amino acid residue, i.e., a cyclosporine, for example cyclosporine of formula (I), which is a residue of (D) -β-acyloxy-α-amino acid. In this method, cyclosporine, for example in formula (III), wherein the amino acid residue at position 8 is a (D) -acyloxy-α-amino acid residue, ie, a (D) -β-hydroxy-α-amino acid residue. Cyclosporin of the compound may be acylated to introduce an R ₁ -CO group at the β-position of the formula (IV), or 1- to generate a corresponding cyclosporine whose residue at the 1-position is -dihydro-MeBmt-. The amino acid residue at position is -MeBmt-, and the residue at position 8 is a (D) -acyloxy-α-amino acid residue, for example cyclosporin, a (D) -β-acyloxy-α-amino acid residue. Reducing, i.e. lowering X to -MeBmt- to produce the corresponding cyclosporin, Xdi-hydro-MeBmt- A method for producing a cyclosporin comprising reducing the cyclosporin of formula (I) as defined in the above. In the above formula (Ⅰ) X is -MeBmt-or-dihydro-MeBmt- Y is -αAbu-, -Ala-, -Thr-, -Val- or -Nva-, Z is -Val- or -Nva- Q is the residue of formula (II), In formula (II) R ₁ is hydrogen, C _1-4 alkyl or phenyl R ₂ is hydrogen or methyl, In the above formula (III) X, Y, and Z are as defined in formula (I), W is the residue of formula (IV), In formula (IV), R ₂ is the same as defined in formula (II). The method of claim 1, wherein X is -MeBmt, Y is -αAbu-, Z is -Val-, and Q is -O-acetyl- (D) Ser-. In preparing the cyclosporine of formula (IIIa), deprotection of the cyclosporine of formula (III) as defined above in the 0-protected form and cyclizing a straight chain undecapeptide containing the sequence Unprotected or zero-protected; When Y 'is -Thr-, -Val- or -Nva-, Z' is -Val- or Y 'is -Nva-, -Nva-, W is-(D) Ser-, X' is -MeBmt- [Thr] ² -cyclosporine [Val] ² -cyclosporine, [Nva] ² -cyclosporine or [Nva], which produces a strain by contacting a nutrient medium containing (D) -serine to produce a cyclosporine of formula (IIIa) ] ² - [Nva] ⁵ - from the culture medium calculated by culturing a cyclosporin separate the cyclosporin of formula (ⅲa) and; A process for producing a cyclosporine of formula (IIIa) wherein X 'comprises reducing the corresponding cyclosporin of -MeBmt- recognition (IIIa) to generate cyclosporine of -dihydro-MeBmt- recognition (IIIa). In the above formula Y 'is -αAbu-, -Thr-, -Val- or -Nva-, Z 'is -Val- or -Nva- when Y' is -αAbu- or -Nva-, W 'is-(D) Ser- or Y' is -αAbu- When Z 'is -Val- then (D) Thr- X 'is -Val- or -Nva- when -MeBmt- or Y' is -Thr- and Z 'is -Val- When Q is-(D) Ser-, it is -dihydro- -MeBmt-. ※ Note: The disclosure is based on the initial application.