Trehazolamine

Feng, X., Duesler, E.N., and Mariano, P.S. (2005) Pyridinium salt photochemistry in a concise route for synthesis of the trehazolin aminocyclitol, trehazolamine. Journal of Organic Chemistry, 70 (14), 5618-5623. 

Trehazolines with Trehazolamines on Positions Other than the Anomeric Center 100... 

Thus, the synthesis of trehazolin and its analogues required two precursors, the glycosyl isothiocyanate or amine analogues thereof, and trehazolamine or isothicya-nate analogues, respectively. 

Fig. 3. Structures of trehalozamine and its analogues. The dot within the structure indicates that the carbon at this position(s) is sterically different from natural trehazolamine.

Efficient syntheses of trehazolamine (5) starting from D-mannose (Scheme 15)79 have been readily achieved by deacetylation of phenyl 1-thio-a-D-mannopyranoside (109),80 followed by monoacetonation under kinetic conditions to give 110. Regio-selective benzylation of the equatorial hydroxyl group of 110 gave 111, whose... 

The tri-O-benzyl trehazolamine 161 has been synthesized from D-arabinose (Scheme 20).89 The precursors 156 and 157 were first prepared from 2,3,5-tri-<9-benzyl D-arabinose 155 in 47% overall yield.88 Removal of the p-methoxybenzyl... 

D-Mannitol was also used as a precursor for trehazolamine via its conversion into the (/ )-(—)-epichlorohydrin (162),91,92 which gave the optically active l-(hydroxy-methyl)spiro[2,4]cyclohepta-4,6-diene (163) in 60% yield upon treatment with lithium cyclopentadienide (Scheme 21).49 Conversion of 163 into the corresponding trichloroacetimidate 164,93 followed by reaction with I(,yy/w-collidine)2CI04, afforded... 

A strategy for the synthesis of trehazolamine has been developed from 1-methox-yethoxymethyl-3-pivaloyloxymethylpyridinium perchlorate via amino cyclopentane derivatives (Schemes 42 and 43).115 Pyridinium salt 351 was prepared by a two-step sequence from 3-(hydrooxymethyl)pyridine 349 via 350 (Scheme 42). Irradiation of 351 in aqueous NaHC03 led to production of the separable bicyclic aziridines 352 (20%) and 353 (16%). Ring opening of 352 by acetic acid, followed by removal of the... 

VII. Synthesis of Trehazolins 1. Trehazolins Having Trehazolamines at the Anomeric Center... 

The synthesis of trehalamines has generally involved the thiourea derivative of trehazolamines by intramolecular cyclization with one of the neighboring hydroxyl groups. Thus, treatment of 88 with benzyl isothiocyanate afforded the thiourea derivative 371. Compound 371 was hydrogenolyzed to cleave the two MOM groups,... 

Treatment of trehazolamine analogue 38 with isothiocyanate 7 in the presence of Et3N afforded 421 in 84% yield. Oxazoline formation from 421 with 2-chloro-3-ethylbenzoxazolium tetrafluoroborate gave 422 (84%), hydrogenolysis of which gave diepimer 416 in 43% yield (Scheme 58).106,107... 

I. S. de Gracia, H. Dietrich, S. Bobo, and J. L. Chiara, A highly efficient pinacol coupling approach to trehazolamine starting from D-glucose,./. Org. Chem., 63 (1998) 5883-5889. 

G. Mehta and N. Mohal, Norbomyl route to cyclopentitols Synthesis of trehazolamine analogues and the purported structure of salpantiol, Tetrahedron Lett., 40 (1999) 5795-5798. 

Two interesting syntheses of trehazolamine [336,337] appeared at the same time, based on a diiodosamarium-promoted reductive carbocyclization. A rapid description of both methods will shed light on this strategy. 

---