Regioselective phosphorylation

A non-specific bacterial acid phosphatase from Shigella flexneri (PhoN-Sf) has been screened for regioselective phosphorylation of primary alcohol(s) of more than 20 different cyclic and acyclic monosaccharides using pyrophosphate as the phosphate donor (O Scheme 61) [368]. These studies have shown that PhoN-Sf is capable of phosphorylating a range of hexoses (D-glucose epimers, glycosides, and C-2 derivatives), pentoses, heptoses, ketoses, and acyclic carbohydrates. 

Examples of the synthesis of phosphite and phosphate esters of sugars are included in a review on trivalent phosphorous acids (Scheme 5). The synthesis of an oxyphosphorane has also been reported (Scheme 6). A strategy for regioselective phosphorylation of aldoses in aqueous solution involves reversible attachment of activated diamidophosphate (DAP). The carbonyl addition prod-... 

A small hbrary of 39 peptides was screened for the regioselective phosphorylation of compound 21 [34]. Each peptide afforded different extents of enantiose-lectivity, highlighting how the secondary structure can play an important role in influencing the stereochemical course of the reaction. Remarkably, peptide 20 afforded the desired product as a single enantiomer with >98% ee (Scheme 5.9). 

A high regioselectivity was observed for both silylation and phosphorylation of various 2,3-dihydro-4//-thiopyrones, affording 2//-thiopyrans 108a-f in almost quantitative yields (83YZ1096 90TL845 91CJC1487). 

Regioselective cyclization of /V-(4-benzoyl-5-benzimidazolyl)amino-methylenemalonates (969, R = H, Me) was observed. When the cyclization was carried out in polyphosphoric acid, then 4-phenylimidazo-[4,5-/]quinoline-5-carboxylates (970) were obtained, while the thermal cyclization in diphenyl ether at 200°C, or the cyclization in a mixture of phosphoryl chloride and polyphosphoric acid afforded 4-benzoyl-8-hydroxyimidazo[5,4-g]quinoline-7-carboxylates (971) (89KFZ692). 

In an aldol condensation an enolate adds to a carbonyl group. Among the various methods which have been developed to achieve regioselectivity those involving polarity alternation accentuation are a time-honored technique. For example, the closure of a more strained diquinane nucleus rather than a hydrindane system is possible by installing a phosphoryl group in the a-position of the appropriate ketone [148]. 

Regioselectivity in the chlorination of pyrazine /V-oxides with phosphoryl chloride depends upon the substituent on the C-3 carbon. Thus, 3-aminopyrazine 1-oxide is chlorinated with loss of the /V-oxide oxygen to give 2-amino-3-chloropyrazine as the sole product whereas 3-methoxy and 3-chloropyrazine 1-oxides form approximately equal amounts of 3-chloro- and 6-chloro-2-substituted pyrazines along with a trace of the 5-chloro derivatives. 

On the other hand, the enzymatic synthesis of glycoconjugates and oligosaccharides leads to high product yields in a short time by stereo- and regioselective one-step reactions. All enzymatic reactions are easy to scale up and are carried out in aqueous media under mild conditions. A whole set of enzymes is now available to build up OAT bonds in monosaccharides, COP bonds in activated monosaccharides e.g. phosphorylated sugars or nucleotide sugars, and C-O-C bonds in di- and oligosaccharides (Fig. 1). However, all these enzymatic reactions are limited by the substrate spectrum of the individual enzyme. 

Almost complete regioselectivity for reaction at C-7 was found when the indoles 20a and 62 were combined with 3-bromo-2-pyrrolidinone 52 and phosphoryl chloride. While traces of the 2-isomers 68a,b were observed, only the latter could be isolated in 3% yield. In contrast, the 7-pyrrolinyl compounds 67a,b were isolated in 65% yield33 (Scheme 20). 

Phosphorylation of a ketone enolate to afford an enol phosphonamide. (See Figure 10.10, bottom row, regarding the regioselectivity of the enolate formation.)... 

Regioselective formylation was also achieved by treatment of a 3-phenylbenzo[3]furan with AiACdimethylforma-mide and phosphoryl chloride (Vilsmeier reagent) at 0-25 °C to give 2-carbaldehyde derivative in 90% yield (Equation 61). In addition, a variety of interesting 2-acylbenzo[/ ]furan derivatives were described in the same article <2002T5125>. 

In contrast, the 2-position of 2,4-dichloroquinazoline is more reactive than the 4-position for the attack by tertiary amines. The reaction of 2,4-dichloroquinazoline with A -substituted cyclic amines thus affords cyclic A,iV-disubstituted 4-chloroquinazolin-2-amines 9 and, in the case of A -methylpyrrolidine, the ring-opened derivative 10. The regioselectivity of this reaction is considered to be determined by the steric nature of 2,4-dichloroquinazoline and is in good accord with that of the reaction of quinazoline-2,4(l//,3//)-dione with A-substituted cyclic amines in combination with phosphoryl chloride (cf. p 121). 

Amidotriphosphate (57) and diamidophosphate (58) are convenient reagents for the regioselective a-phosphorylation of aldoses in aqueous solution. 

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