Phospha sugars

Keywords Phospha sugar Phosphorus heterocycle P - C compound Phospholene Phospholane... 

These phospha sugar analogues are acetylated into 49a-d and the structure of the acetates of the phospha sugars are analyzed by NMR spectrometry to elucidate the conformation (Table 1). 

D-Ribofuranose-type phospha sugars 50 (R=OH, Et, and Ph) and 2-deoxy-D-ribofuranose analogues 51 (R=OH and Me) in Fig. 3 have been prepared via longer reaction pathways by a similar ring closing intramolecular addition reaction of a P - H group to an aldehyde of sugars shown in Scheme 14 [17-20]. 

To improve the preparative method of phospha sugars from sugar starting materials [21,22], the Arbzov reaction and Grignard coupling reaction have been applied to a reaction of 1,4-dibromobutane. The reaction of 1,4-dibromobutane (53) with dimethyl phenylphosphonite to give ethyl (4-bromobutyl)phenylphosphinate (54) and successive intramolecular substitution of the 4-bromo substituent with phosphinyl anion affords 1-phenyl -phospholane 1-oxide (56a) in 40% yield. It can also be prepared from... 

Novel preparative methods for phospha sugars (e.g., 74-77, 83, 89-91) and/or phosphorus heterocycles (up to now phospha sugars have not been found in natural products) have been extensively developed starting from phosphorus heterocycles such as phospholenes, unlike traditional sugar chemistry in which sugar starting materials (e.g., 72,78,94,92,93) are mainly used (Schemes 22-25) [30-33]. 

Scheme 22 Novel preparative methods for phospha sugars 74-77...

The structure of 93a was elucidated by X-ray single crystal structure analysis to be the 6-dcoxy-D-g/wco-typc phospha sugar (Fig. 5). 

Using the new preparative method, combined with reactions at the allylic position in the phospholene 1,2,3,4-tetrasubstituted-phospholanes, a series of the tetrofuranose-type phospha sugars can be prepared (Scheme 28 and Tables 3 and 4) [37,38]. 

Scheme 28 Preparation of a series of tetrofuranose-type phospha sugars...

Scheme 29 Preparation of phospha sugar AT-glycosides 104Ea-d...

Phospha sugar nucleosides have not yet been shown to be naturally occurring. Some analogues of phospha sugar nucleosides (e.g., 118) are prepared from 2-bromo-3-hydroxyphospholanes 94 or 103 by nucleophilic substitution reaction with nitrogen nucleophiles (Schemes 35 and 36, and Table 8). However, the nucleophilic substitution reaction (or electrophilic substitution reaction in the presence of catalyst) of 2-bromo-3-hydroxyphospholanes 94... 

Scheme 35 Preparation of phospha sugar nucleoside 118 from 2-bromo-3-hydroxyphos-pholane 103 by nucleophilic substitution reaction with nitrogen nucleophiles...

Table 8 Preparation of phospha sugar nucleoside 118 by the reaction of 2-bromophos-pholane 103c with cyclic base 117...

Scheme 37 Nucleophilic substitution reaction of 2-bromo-3-hydroxyphospholane 103a with nucleic acids does not give phospha sugar nucleosides...

Scheme 38 Alternative preparative method for phospha sugar nucleosides a NaN3, DMF, 70 °C, 24 h b substituted acetylenes (R CCR2 are shown in Table 9), DME, reflux...

Scheme 39 Synthesis of pyrimidine or uracil nucleosides of phospha sugars...

Table 10 Deoxy phospha sugar pyrimidine nucleosides 120a-g prepared via Scheme 39...

Scheme 40 Preparation of amino acid derivatives of phospha sugars 124a-h...

From 3-phospholenes 95, pentofuranose- and hexofuranose-type phospha sugars are prepared. Thus, all four kinds of pentofuranose-type phospha sugars (i.e., xylose, lyxose, ribose, and arabinose) are available from 3-phos-pholene as the starting material. Alkylation of 95 by a Cl unit provides the pentofuranose structure. The alkylation under LDA base and alkyl halides proceeds to give 130 (Table 13), whose czs-dihydroxylation affords 131. The... 

The pentofuranose-type phospha sugar 132 is converted into the acetonide 133, whose structure determined by X-ray analysis is represented in Fig. 20. 

Scheme 44 Preparation of phthalated phospha sugars 137-136 by nucleophilic substitution reaction with potassium phthalimide...

Scheme 46 Preparation of a-D-xylo- and -D-lyxo furanose-type phospha sugars 137X and 137L from 135a...

Scheme 47 Preparation of a-v-ribo- and p-D-arafeino-pentofuranose-type phospha sugars 144R and 144A from 135b...

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