| US RE40,040 E1 | ||
| Process of use in converting the 4″(S)-OH functional group of the cladinose unit of an azamacrolide to 4″(R)-NH2 | ||
| Patrick Leon, Lyons (France); Frederic Lhermitte, Saint Symphorien d'Ozon (France); Ronan Guevel, Lyons (France); Denis Pauze, Lyons (France); Laurent Garel, Lyons (France); and Gilles Oddon, Lyons (France) | ||
| Assigned to Merial Limited, Duluth, Ga. (US) | ||
| Filed on Sep. 09, 2005, as Appl. No. 11/223,912. | ||
| Application 11/223912 is a reissue of application No. 09/484648, filed on Jan. 18, 2000, now 6,353,096, filed on Mar. 05, 2002. | ||
| Claims priority of provisional application 60/127400, filed on Apr. 01, 1999. | ||
| Claims priority of application No. 99 00459 (FR), filed on Jan. 18, 1999. | ||
| Int. Cl. C07H 1/00 (2006.01); C07H 17/08 (2006.01) | ||
| U.S. Cl. 536—7.4 [536/18.5] | 32 Claims |
1. A process for the stereoselective preparation of a compound of formula I  wherein:
R is a hydrogen atom or a C1-C10 alkyl, C2-C10 alkenyl or C6-C12 arylsulphonyl group, optionally substituted;
A, each of which is identical or different, is
a hydrogen atom,
a nitrogen atom, optionally substituted,
a C1-C4 alkyl group, which is optionally substituted by one or more aryl groups, which are, in turn, optionally substituted,
an R2CO or R2SO2 group, with R2 being a hydrogen atom, a C1-C8 alkyl group or an aryl group, which are, optionally substituted; and
∇ indicates that the C in the 4″ position has undergone an inversion of configuration
with respect to the formula II, from a compound of formula II:
 wherein:
R as defined in formula I and
P1 is a protective group for the hydroxyl functional group at the 2′ position, comprising the steps of:
(i) activating the hydroxyl functional group at the 4″ position in the compound of formula II, in order to obtain a compound
of formula III:
 wherein:
R and P1 are as defined in formulae I and II and
OR1 is a leaving group;
(ii) contacting the compound of formula III with a nitrogenous nucleophilic derivative under conditions which are sufficient
to allow the stereoselective displacement of the hydroxyl functional group activated by the said nitrogenous nucleophile;
and
(iii) deprotecting the hydroxyl functional group at the 2′ position.
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