Sugar-derived nucleophiles

A nitro group can alternatively be introduced in a sugar by nucleophilic displacement of iodide by a nitrite ion. This procedure was recently used in the preparation of the L-idose derived nitro sugar 14, an intermediate in the synthesis of polyhydroxylated cispentacin analogues (Scheme 6).15... 

Rauter s group exploited the synthesis of sugar derived bicyclic butenolides ( e.g. 140, Fig. 44),60 which possess cytotoxic and antitumor activities. The key structural feature of such compounds consists of the presence of the a,(3-unsaturated lactone, which allows them to act as Michael acceptors for the addition of enzymes nucleophiles. 

MgBr2-mediated asymmetric nucleophilic addition of Grignard reagents and allyl-tributyltin to aldehydes bearing sugar-derived jS- or y-tetrahydropyranyloxy chiral auxiliaries designed to complex with MgBt2 has been achieved. ... 

An example of a sugar-derived chiral -haloketone is offered by 24. When ulosyl bromide 24 is coupled to acetaldehyde in a Grignard-type process, a mixture of isomeric adducts is formed, where the 50% is represented by 25, possessing the (R) configuration at the hydroxy ethyl substituent (equation 21). The same protocol is applied in an efficient nucleophilic C-glycosidation reaction of 24 with galactose-derived aldehyde 26 to give 27 (equation 22)20. 

By far, the most challenging task in bond-forming reactions with sugar derivatives is to effect C—C branching. The 2 nucleophilic displacement reactions with carbon nucleo-... 

Three types of lyases have been identified that catalyze the addition of phosphoenolpyruvate (PEP) to aldoses or to terminally phosphorylated sugar derivatives. With simultaneous release of inorganic phosphate from the preformed enolpyruvate nucleophile during C-C bond formation the additions are essentially irreversible and, therefore, these lyases are often referred to as synthases. The mechanistic details of these reactions, however, have yet to be elucidated but it seems obvious that the chances of variation on the part of the nucleophile will be strictly limited. Although the thermodynamic advantage makes these enzymes highly attractive for synthetic applications, none of them is yet commercially available and only few data have been reported concerning the individual specificities towards aldehydic substrates. 

Heteropolyacids are also active for the conversion of sugar derivatives (360). H XMi2O40 (X = P, Si, M = W, Mo) are much more active than conventional catalysts such as p-toluenesulfonic acid and ZnCl2 for nucleophilic substitution... 

This kind of behavior towards nucleophilic reagents is the basis for the many fascinating transformations which can be brought about with sugar derivatives through appropriate treatment of their sulfonic esters. 

Epoxy sugars are frequently used as starting compounds in the synthesis of sugar derivatives (compare Section IV) such as halo, amino, azido, thio, deoxy, and branched-chain derivatives. The oxirane ring is in general more reactive than the oxetane or oxolane ring. It is opened with nucleophiles under base or acid catalysis. On the other hand, the oxirane ring remains unattacked under the conditions of catalytic debenzylation on palladium,... 

C(6) to give an oxonium ion. Nucleophilic attack, probably by acdtic acid, on the benzylic carbon gives a O-acetyl sugar derivative and benzyl acetate. Glycosides are also acetolysed under these reaction conditions. 

Alternatively, Pd(0) adds oxidatively to the double bond of a glycal derivative resulting in the formation of a ir-allyl complex, which may react with carbon nucleophiles to give C-glycosides with a double bond between C(2) and C(3).26 A rt-allyl complex may also be formed starting from a Ferrier rearrangement product (2,3-unsaturated sugar derivative).22... 

In the previous subsection, it was shown that the Ferrier reaction offers an opportunity to convert glycal derivatives into unsaturated sugar derivatives, which have an isolated double bond between C(2) and C(3). The Tipson-Cohcn reaction is another important reaction for the introduction of isolated double bonds.29 In this procedure, a cis or tram diols are converted into disulfonates (mesylates or tosylates) which are reductively eliminated with sodium iodide and zinc in refluxing DMF (Scheme 3.6a). In this reaction, the C(3) sulfonate is substituted by an iodide, which then is reductively removed by zinc with concomitant elimination of the second sulfonate moiety, introducing a double bond. Stereoelectronic effects make nucleophilic substitutions at C(3) more favourable than similar reactions at C(2) (see Section 3.2.3). Probably, the elimination proceeds through a boat conformation. In this case, the iodide and tosylate are in a syn relation. In most cases, E2 elimination proceeds via a transition state involving an anti orientation. Nevertheless, syn elimination becomes the dominant mode of reaction when structural features prohibit an anti orientation. 

Azide ions are by far the most common nucleophilic species employed in substitution reactions for the preparation of amino sugars. An azido moiety is stable under many reaction conditions but can be reduced to an amino group by a variety of reagents. The nucleophilicity of azido ions can be increased by the addition of a suitable crown ether to complex the counterion.36c,63b In the past, ammonia and hydrazine were used as nucleophiles to overcome unfavourable dipolar interactions that arise when charged nucleophiles were used. However, a drawback of the use of these nucleophiles is that the product is still nucleophilic and can perform a second displacement. Phthalimide ions have successfully been applied in displacement reactions to yield a protected amino sugar derivative.58 63f... 

Nucleophilic ring opening of epoxy sugars is a valuable method for the synthesis of many modified sugar derivatives. The reaction is accompanied by Walden inversion, and a wide range of nucleophiles can be used. The cyclic nature of epoxides renders the competing elimination process stereoelectronically unfavourable. For asymmetric epoxides, in principle, two regio-isomeric products can be formed however, in... 

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