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Among the C6 halo purine ribonucleosides, the readily accessible 6-chloro derivative has been known to undergo slow SNAr reactions with amines, particularly aryl amines. In this work, we show that in 0.1 M AcOH in EtOH, aryl amines react quite efficiently at the C6 position of 2’,3’,5’-tri-O-(t-BuMe2Si)-protected 6-chloropurine riboside (6-ClP-riboside), with concomitant cleavage of the 5’-silyl group. These two-step processes proceeded in generally good yields and notably, reactions in the absence of AcOH were much slower and/or lower yielding. Corresponding reactions of 2’,3’,5’-tri-O-(t-BuMe2Si)-protected 6-ClP-riboside with alkyl amines proceeded well but without desilylation at the primary hydroxyl terminus. These differences are likely due to the acidities of the ammonium hydrochlorides formed in these reactions, and the role of AcOH was not desilylation but possibly only purine activation. With 50% aqueous TFA in THF at 0 oC, cleavage of the 5’-silyl group from 2’,3’,5’-tri-O-(t-BuMe2Si)-protected N6 alkyl adenosine derivatives and from 6-ClP-riboside was readily achieved. Reactions of the 5’-deprotected 6-ClP-riboside with alkyl amines proceeded in high yields and under mild conditions. Because these complementary methodologies yielded N6 aryl and alkyl adenosine derivatives containing a free 5’-hydroxyl group, a variety of product functionalizations was undertaken to yield N6,C5’ doubly modified nucleoside analogues.
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Synthesis of carbohydrate building blocks via regioselective uniform protection/deprotection strategies
Discussed herein is the synthesis of partially protected carbohydrates by manipulating only one type of a protecting group for a given substrate. The first focus of this review is the uniform protection of an unprotected starting material in a way that only one (or two) hydroxyl group remains unprotected. The second focus involves regioselective partial deprotection of uniformly protected compounds in a way that only one (or two) hydroxyl group becomes liberated.
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- Award ID(s):
- 1800350
- PAR ID:
- 10095965
- Date Published:
- Journal Name:
- Organic & Biomolecular Chemistry
- Volume:
- 17
- Issue:
- 20
- ISSN:
- 1477-0520
- Page Range / eLocation ID:
- 4934 to 4950
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Carbohydrate derived low molecular weight organogelators are interesting compounds with many potential applications. Selective functionalization of the different hydroxyl substituents on d -glucose and d -glucosamine resulted in small molecular gelators. Previously we have found that the C-2 acylated derivatives including esters and carbamates of 4,6- O -benzylidene protected glucose and glucosamine derivatives have shown remarkable applications as molecular gelators. In this research, in order to probe the structural influence of sugar derivatives on molecular self-assembly, we introduced acylation functional groups to the 3-hydroxyl group of 4,6- O -benzylidene acetal protected N -acetyl glucosamine derivatives. A library of fourteen ester derivatives was synthesized and characterized. The ester derivatives typically formed gels in pump oil and aqueous mixtures of dimethyl sulfoxide or ethanol. The resulting gels were characterized using optical microscopy, and rheology, etc. All alkyl ester derivatives were gelators for pump oil. A short chain ester derivative was able to form gels in a few different oils and the corresponding oil water mixtures phase selectively. The compound was also used to trap naproxen sodium and formed a stable co-gel. The controlled release of the drug from the gel to the aqueous phase was analyzed using UV-vis spectroscopy. These results show that the functionalization at the 3-OH position of the N -acetyl glucosamine derivative is a feasible strategy in designing new classes of organogelators.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/c9ob00573k
