2-Amino-3-hydroxy-4-methyl-6-octenoic acid

Table 1.2. CHEMICAL STRUCTURES OF CYCLOSPORINS A-Z Bmt = (2S, 3R, 4R, 6 -2-amino-3-hydroxy-4-methyl-6-octenoic acid (= (4R)-4-(( )-2-butenyl)-4-methyI-L-threonine) Abu = L-a-aminobuty-ric acid Nva = L-norvaline MeVal = V-methyl-L-valine MeLeu = A -methyl-L-leucine. 

The occurrence of numerous secondary metabolites and the unusual structural elements l-a-aminobutyric acid, D-alanine, and the C9-amino acid (2S,3/(,4/(,6 )-2-amino-3-hydroxy-4-methyl-6-octenoic acid [(4/ )-4-(( )-2-butenyl)-4-methyl-L-threonine=Bmt] indicate that this peptide is not produced ribosomally but rather post-translationally by a multi-enzyme complex. Additionally offered foreign amino acids are incorporated, e.g., further cyclosporins are obtained in directed biosyntheses by replacement of the a-aminobutyric acid in position 2 by D- or L-allylglycine, of d-alanine in position 8 by D-setine or 3-fluoroalanine, and of butenylmethylthreonine in position 1 by L-/S-cyclohexylalanine... 

Ecample Miller and Rich investigated the conformational consequences of substitutions on an amino acid in cyclosporin A, an important immunosuppressive drug. One of the amino acids in this cyclic undecapeptide is (2, 3r, 4r, 6e)-3-Hydroxy-4-methyl-2-(methylamino)-6-octenoic acid (MeBmt). It is essential for biological activity. 

This type of yvn-seleclivc aldol addition has been applied in the synthesis of the unusual L-threonine based amino acid, (2,S, 3/ ,6F)-3-hydroxy-4-methyl-2-methylamino-6-octenoic acid, of cyclosporine104, of the cyclic hexapeptide echinocandin105, and of the antibiotic ionomycin97. 

J )-hydroxy-4(J )-methyl-6( )-octenoic acid or its thioester into the 2-amino derivative remains to be analyzed. 

Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoic acid 4,ll-bis[(2-Aminoethyl)amino]anthra[2,3-b]furan-5,10-diones 4(l-Anilino-podophyllotoxin derivatives 5-Aza-2 -deoxycytidine 5-Bromotetrandrine 5-Cyclohexylindolyl-2 -deoxyribose (non-natural nucleoside) 5 -Fluorosulfonylbenzoyl 5 -adenosine 5-Fluorouracil 5,5-Diphenylbarbituric acid 6-[(2S,4R,6E)-4-Methyl-2-(methylamino)-3-oxo-6-octenoic acid] cyclosporine D (PSC833) 6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid 6-Mercaptopurine 6-Prenylchrysin 6-Thioguanine 6,7-Dimethoxy-... 

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