Download PDF
Synthesis 2003(15): 2378-2384  
DOI: 10.1055/s-2003-42437
PAPER
© Georg Thieme Verlag Stuttgart · New York

Discriminative Glycosylation of 3-(Aryloxy)propane-1,2-diols by Choice of a Glycosyl Donor

Hari Babu Mereyala*a, Sreeman Kumar Mamidyalaa, Krishna Prasad Chigurupatib, Sastri R. Srinivasab
a Speciality, Gas Based Chemicals and Processes Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India
Fax: +91(40)27160921; e-Mail: mereyalahb@rediffmail.com;
b Granules India Ltd, Road No.2, Banjara Hills, Hyderabad 500 033, India
Further Information

Publication History

Received 21 May 2003
Publication Date:
23 October 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

Regioselective glycosylation of rac-guaifenesin (1A) with various glycosyl donors viz., β-d -glucosepentaacetate (2), pyridyl 2,3,4,6-O-tetra-O-benzyl-1-thio-β-d-galactopyranoside (9), 1-O-acetyl-2,3,5-tri-O-benzoyl-α/β-d-ribo- (13) and xylofuranoside (17) is reported. Glycosyl donors 2, 13 and 17 bearing ester protecting groups is reported to exhibit high regioselectivity to form the corresponding diastereomeric mixture of 1-O-glycosylated guaifenesin derivatives 3A, 14A and 18A, respectively; formation of diglycosylated derivatives 5A, 15A and 19A is not observed. While no such selectivity is observed when the donor 9 bearing ether protecting groups is used in the coupling reaction with 1A, resulting in the formation of digalactosylated derivatives 10A. That the regioselectivity is not dependent upon substituents present on the aromatic ring is shown by coupling 1B with 2 to isolate 1-O-glycosylated derivative 3B; formation of diglycosylated derivative 5B was not observed. Applicability of this finding is shown by preparation of enantiopure guaifenesin [(R)-1 (98% ee) and (S)-1 (98% ee)] by separation of their corresponding diastereomers (R)-3 and (S)- 3, respectively.

Key words

regioselective glycosylations - 3-(aryloxy)propane-1,2-diols - glycosyl donors - guaifenesin - resolution