7 Some Aspects of the Chemistry of D-Glucal
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I. D. BLACKBURNE, A. I. R. BURFITT, P. F. FREDERICKS, and R. D. GUTHRIE School of Science, Griffith University, Nathan, Q.4111, Australia
D-Glucal (Fig. 1) is a well known unsaturated sugar (1) in the words of Fraser-Reid (2) "venerable". There has been much study of the chemistry of this compound, and of its stereo -isomers, D-galactal etc., as witnessed by work described in the excellent reviews in Advances in Carbohydrate Chemistry by Ferrier (3,4) and its continuing mention in the Specialist Periodical Reports on Carbohydrate Chemistry. Not unexpectedly much of the research on D-glucal has involved addition of a wide variety of molecules to the 1,2-double bond (3,4). Little work has been done to exploit the other feature of D-glucal, namely that it has three different types of hydroxyl group, primary, secondary, and allylic. (Fig. 1) Those few derivatives at the 3,4 or 6 position that have been made have been prepared from the appropriate D-glucose compound then finally putting the 1,2-double bond in place. No studies have been made, as far as we are aware, of the selectivity of reaction amongst the three hydroxyl groups. This exploitation of D-glucal chemistry has "relevance" as a l l our work is nowadays supposed to have. Amino-glycoside antibiotics (5) are now important chemotherapeutic substances. The nitrosyl chloride based synthesis devised by Lemieux (Fig. 2) is of particular interest here as it utilises glucals in the synthesis of α-linked glycosides with an amino or an hydroxyl group at C-2. Thus one could envisage a semi-synthetic route to modified kanamycins. (Figs. 3 and 4) These suppose that D-glucal derivatives with required modification at C-3 or C-6 (Fig. 5) are available: such compounds are our targets. We decided f i r s t to investigate the synthesis of 6-deoxy-6-fluoro derivatives. 3,4-Di-0-benzoyl-6-0-tosyl-D-glucal (Fig. 6) is probably the most readily available (7) potential starting material. Reaction with fluoride ion in protic solvents such as ethylene glycol led to products that were difficult to separate. Caesium fluoride in DMF, in contrast gave a beautifully crystalline compound, (92%) which was identified as the novel 116
In Synthetic Methods for Carbohydrates; El Khadem, H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1977.
7.
BLACKBURNE E T A L .
Chemistry
of
Ό-Glucal
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Figure 1. Ό-Glucal, showing, from top to bottom, a pri mary, secondary, and an allylic hydroxyl group
In Synthetic Methods for Carbohydrates; El Khadem, H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1977.
117
118
SYNTHETIC
METHODS
FOR
CARBOHYDRATES
Downloaded by IMPERIAL COLLEGE LONDON on February 18, 2015 | http://pubs.acs.org Publication Date: June 1, 1977 | doi: 10.1021/bk-1977-0039.ch007
NHR'
Figure 4
HO- -
Figure 5
HO
TsO—ν
/ \
0coo- -
