Patent ID: 8203005

Claim:
A process for the preparation of a compound of general formula I wherein R 1 represents hydrogen, linear or branched C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, alkylaryl, arylalkyl, or acyl or carbamoyl, trifluoracetyl, mesyl, tosyl, trifluoromethanesulfonyl, trialkylsilyl or alkylarylsilyl; R 4 represents hydrogen, arylalkyl, alkoxy, arylalkoxy, trialkylsilyl, alkylarylsilyl, with heteroatom(s) substituted arylalkyl, or other N-protective group; R 5 represents hydroxy, linear or branched C 1-6 alkyloxy, aryloxy, alkylaryloxy, arylalkyloxy, trialkylsilyloxy or alkylarylsilyloxy, halogen, —NH 2 , —NMe 2 , —NHCH 2 C(CH 3 ) 2 CONH 2 R 6 represents hydrogen, arylalkyl, trialkylsilyl, alkylarylsilyl, with heteroatom(s) substituted alkyl, arylalkyl, or other O-protective group; comprising following steps: a) reaction of the compound of formula II, wherein R 2 represents hydrogen, alkyl, aryl, alkylaryl, arylalkyl, trialkylsilyl, alkylarylsilyl, with heteroatom(s) substituted alkyl, aryl, alkylaryl, arylalkyl, or other O-protective group, either aa) with acetone under basic conditions followed by dehydration step providing the compound of formula III followed then by reduction or hydrogenation of the double bond or or bb) with a strong organic or inorganic base, preferably organic lithium or sodium amide as e.g. LDA, or LiHMDS or NaHMDS, followed by alkylation with isopropyl halide, preferably bromide or iodide, providing compound of formula IV b) reaction of the compound of formula IV with a compound of formula V, wherein R 1 is the same as defined for compound of formula I and R 3 is a metal containing group such as —Li, —Na, —Mghalide, Znhalide, —Cehalides, boronic acid as —B(OH) 2 , cuprate or —Cuhalide, providing a compound of formula VI c) hydrogenation or/and reduction of C(8)-oxo and C(5)-hydroxylamine group in the compound of formula VI, either simultaneously or in separate steps, to a compound of formula VII, wherein R 1 is the same as defined for compound of formula I and R 4 is hydrogen, trialkylsilyl, alkylarylsilyl; d) protection of the C(5)-amino group, followed by either aa) hydrolysis of the lactone of formula VII and subsequent reaction of the free carboxylic acid with a peptide coupling reagent and then reaction with R 5 —H, wherein R 5 is the same as defined for the compound of formula I, or bb) by direct reaction of the lactone of formula VII with R 5 —H.