1. Field of the Invention
The invention concerns .alpha.-thiolincosaminide derivatives; their preparation and uses as intermediates in the chemical synthesis of lincomycin analogs. More particularly, the invention concerns novel alkyl N-acyl-6,7-aziridino-6-deamino-7-deoxy-.alpha.-thiolincosaminides and novel alkyl 7(S)-acyloxythioalkyl-.alpha.-thiolincosaminides, their preparation and use.
2. Description of the Prior Art
7-0-Alkyl-substituted-.alpha.-thiolincosaminides and their preparation from alkyl N-acyl-6,7-aziridino-.alpha.-thiolincosaminides are described in U.S. Pat. No. 3,702,322.
Iranian Pat. No. 10,460 of Aug. 15, 1972 (copending U.S. application Ser. No. 237,129; filed Mar. 22, 1972, now Pat. No. 3,790,560) describes alkyl 7-deoxy-7-mercaptoalkylthio-.alpha.-thiolincosaminides, their preparation by sulfidolysis of appropriate 6,7-aziridino-6-deamino-7-deoxy-.alpha.-thiolincosaminides and their conversion to corresponding lincomycin analogs.
Iranian Pat. No. 10,395 of Aug. 15, 1972 (copending U.S. application Ser. No. 198,990; filed Nov. 15, 1971, now abandoned) discloses alkyl 7-deoxy-.alpha.-thiolincosaminides having a variety of substituted thio groups in the 7(S)-position, such as for example, alkylthio, hydroxyalkylthio and acetoxyalkylthio groups. Also disclosed are preparative procedures for such compounds, which comprises sulfidolysis of appropriate 6,7-aziridino-6-deamino-7-deoxy-.alpha.-thiolincosaminides and use of the product compounds to prepare lincomycin analogs.
Iranian Pat. No. 10,407 of Aug. 15, 1972 (copending U.S. application Ser. No. 199,046; filed Nov. 15, 1971, now U.S. Pat. No. 3,767,649) discloses in particular the compound methyl N-acetyl-2,3,4-tri-0-acetyl-7(S)-[3-(3-acetoxypropylthio)propylthio]-7-deo xy-.alpha.-thiolincosaminide and lincomycin analogs thereof. The patent teaches preparation of the particular compound by addition of trimethylene sulfide to methyl N-acetyl-2,3,4-tri-0-acetyl-6,7-aziridino-6-deamino-7-deoxy-.alpha.-thioli ncosaminide.
In general, the compounds of the present invention are intermediates for preparing many of the compounds disclosed in the above described Iranian patents. None of the intermediate compounds of my present invention can be prepared by the process set forth in the above described patents.
The process of the invention comprises, broadly, the sulfidolysis of certain alkyl 6,7-aziridino-6-deamino-7-deoxy-.alpha.-thiolincosaminide employing a particular class of cyclic sulfur compounds. The products of the process are obtained in very high yields, about twice the yields of sulfidolated products obtained in those processes of Iranian Pat. Nos. 10,395; 10,407 and 10,460, supra.
Since the 7(S)-S-substituted compounds obtained by the process of this invention are quantitatively converted upon hydrolysis to certain of those sulfidolated products of said Iranian Patents, the process of the present invention and the products thereof offer a commercially advantageous means of preparing 7(S)-thiosubstituted lincomycins.
Moreover, the process of the invention provides a method of obtaining intermediate compounds useful for preparing a class of antibacterial agents not previously known, or preparable by previously known methods; i.e., the alkyl N-(L-2-pyrrolidincarboxyacyl)-7-deoxy-7(S)-(acetoxymethoxy)-alkylthio-.alp ha.-thiolincosaminides, and the alkyl N-(L-2-pyrrolidinecarboxacyl)-7-deoxy-7(S)-acetoxymethylthio)-alkylthio-.a lpha.-thiolincosaminides.
Alkyl N-carboxacyl-6,7-aziridino-6-deamino-7-deoxy-.alpha.-thiolincosaminides have also been disclosed prior hereto; see for example, U.S. Pat. Nos. 3,671,647 and 3,702,332; Iranian Pat. Nos. 10,395 and 10,460. However, attempts to obtain the alkyl N-(L-2-pyrrolidinecarboxacyl)-6,7-aziridino-6-deamino-7-deoxy-.alpha.-thio lincosaminides of the invention by methods taught in the above references for preparing the N-carboxacyl analogs, i.e., by N-acylation of the aziridino with an L-2-pyrrolidine-carboxylic acid or the corresponding 1-alkyl substituted L-2-pyrrolidinecarboxylic acid have met with failure prior hereto. By the novel process disclosed herein, alkyl N-(1-carbobenzoxy-4-alkyl)-6,7-aziridino-6-deamino-7-deoxy-.alpha.-thiolin cosaminides are prepared, from which the corresponding useful 1'-hydrogen and 1'-alkyl analogs are obtained.