Current Organic Chemistry

ISSN: 1385-2728

Current Organic Chemistry
Volume 10, Number 6, April 2006

Contents

Current Organic Chemistry Devoted to Carbohydrate Chemistry
Guest Editor: Zbigniew J. Witczak


Editorial Pp. 623


From Exocyclic-Olefinic Carbohydrate Derivatives to Functionalized Carbocyclic Compounds Pp. 625-642
Jian Zhou, Guannan Wang, Li-He Zhang and Xin-Shan Ye
[Abstract]


Sugar Derived Crown Ethers and Their Analogs: Synthesis and Properties Pp. 643-662
Slawomir Jarosz and Arkadiusz Listkowski
[Abstract]


Major Groove Recognition of DNA by Carbohydrates Pp. 663-673
Bert Willis and Dev P. Arya
[Abstract]


Carbohydrate Chemistry for RNA Interference: Synthesis and Properties of RNA Analogues Modified in Sugar-Phosphate Backbone Pp. 675-692
Eriks Rozners
[Abstract]




Abstracts
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Editorial

Welcome to the fifth special issue of Current Organic Chemistry devoted to carbohydrate chemistry.^1-5 As we witness unprecedented growth and interest in the subject, from the introduction of glycobiology through the molecular recognition of carbohydrates, and their supramolecular chemistry, the idea to continue to cover these diversified topics is one of the great temptations.

The aim is to present authorative overviews of the current status of structural and synthetic carbohydrate chemistry, which we perceive to be central to the study of carbohydrate chemistry.This issue also intends to strengthen the steadily increasing understanding of the roles of carbohydrates in nature and the life sciences, in particular.

This jubilee issue (enriched with DNA topics) is a collection of reviews by internationally recognized experts, which are compiled sequentially in order of their importance. The first review, entitled “From Exocyclic-Olefinic Carbohydrate Derivatives to Functionalized Carbocyclic Compounds” by Professor Xin-Shin Ye and co-workers Jian Zhou, Guannan Wang (State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China), examines significant information published thus far on the topic of utilization of functionalized exocyclic-olefinic carbohydrates as universal templates to carbocyclic compounds.

The second review contribution by Professor Slawomir Jarosz and Dr Arkadiusz Listkowski (Institute of Organic Chemistry, Polish Academy of Science, Warsaw, Poland) describes a new carbohydrate chemistry challenge: “Sugar Derived Crown Ethers and Analogs: Synthesis and Properties”. The review covers many various new aspects of crown chemistry as applied to synthetic carbohydrate chemistry.

The fundamentally important topic of DNA recognition has been an enduring theme in the life science of carbohydrate chemistry: Professor Dev Arya and Dr. Bert Willis (Clemson University, South Carolina, U.S.A) set out the principles and procedures for these endeavors and contribute a review on “Major Groove Recognition of DNA by Carbohydrates”

Finally Professor Eriks Rozners (Department of Chemistry, Northeastern University, Boston, U.S.A) contributes a review of “Carbohydrate Chemistry for RNA Interference: Synthesis and Properties of RNA Analogues Modified in Sugar-Phosphate Backbone”. This critically important topic is often unappreciated by synthetic carbohydrate chemists and by highlighting the significance of these physicochemical properties of carbohydrates should give a better understanding and appreciation of carbohydrates.

I kindly thank all the authors for their diligent efforts in producing such an informed and enlightened collection for this jubilee issue and I welcome suggestions and ideas for topics of future issues.

Zbigniew J. Witczak
Department of Pharmaceutical Sciences
Nesbitt School of Pharmacy, Wilkes University
Wilkes-Barre, Pennsylvania 18766

1. Curr. Org. Chem. 4, (5), 455, 2000.
2. Curr. Org. Chem. 4, (6), 565, 2000.
3. Curr. Org. Chem. 5, (12), 1177, 2001.
4. Curr.Org. Chem. 7, (1), 1, 2003.
5. Curr. Org. Chem. 8, (4), 1, 2004.


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From Exocyclic-Olefinic Carbohydrate Derivatives to Functionalized Carbocyclic Compounds
Jian Zhou, Guannan Wang, Li-He Zhang and Xin-Shan Ye

As the structural constituents of many naturally occurring molecules, synthesis of functionalized carbocyclic derivatives has been widely investigated. Among numerous approaches to construct carbocyclic compounds, there is an efficient way of forming carbocyclic derivatives by the use of various monosaccharides as chiral building blocks. In this review, synthetic conversions to functionalized carbocyclic compounds from exocyclic-olefinic saccharides and their applications to synthesis of some natural products or natural product-like analogues will be discussed. The emphases will be put on the latest methodology developments of ring-conversion rearrangement reactions catalyzed by metal catalysts.


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Sugar Derived Crown Ethers and Their Analogs: Synthesis and Properties
Slawomir Jarosz and Arkadiusz Listkowski

Receptors with the sugar unit incorporated into the macrocyclic structure – their synthesis and complexing abilities – are reviewed. The receptors with the disaccharide moieties (although such derivatives are rare) including sucrose are also described in this review.


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Major Groove Recognition of DNA by Carbohydrates
Bert Willis and Dev P. Arya

Because of the number of distinguishable interactions within the DNA major groove, there is considerable interest in discovering the governing factors involved in DNA recognition. Carbohydrates represent a class of DNA-interactive agents capable of binding the major groove due to their size and intricate distribution of hydrophobic and hydrophilic interactions within their molecular structure. To date a limited number of carbohydrates have been found to interact within the DNA major groove; the majority have been shown to bind within the minor groove. Representative carbohydrates that bind within the major groove include neocarzinostatin, nogalamycin, and a few aminoglycoside (neomycin) conjugates developed in our labs. An overview of the various DNA groove-binding carbohydrates is presented, with particular emphasis on novel aminoglycoside-based approaches in probing the molecular environment and requirements therein associated with the DNA major groove.


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Carbohydrate Chemistry for RNA Interference: Synthesis and Properties of RNA Analogues Modified in Sugar-Phosphate Backbone
Eriks Rozners

The recent discovery of RNA interference (RNAi) as an efficient and naturally occurring mechanism of gene regulation has revitalized interest in chemically modified RNA analogues. For potential in vivo applications, either in pre-clinical settings or as therapeutic agents, small interfering RNAs (siRNAs) will require chemical modifications to fine-tune the thermal stability and increase potency, cellular uptake, and in vivo half-life of the siRNA duplexes. Moreover, chemical modifications may be able to address such difficult and long-standing problems as biodistribution and cell type selective targeting of siRNA. Modern synthetic carbohydrate chemistry is excellently positioned to address the needs of the RNAi community relevant to chemically modified siRNAs. The present article reviews synthesis and properties of sugar-phosphate backbone modifications already used or potentially useful for RNAi applications. Modifications in the sugar moiety only (e.g., 2'-O-alkyl and aminoalkyl RNA) and RNA having the entire sugar-phosphate backbone altered (e.g., formacetal and amide-linked RNA) will be discussed. Synthetic routes and biophysical properties of these analogues will be reviewed. Current and potential future applications of modified RNA in fundamental biochemical research and biomedicine, with emphasis on RNA interference, will be briefly discussed.