Note Synthesis of 2,3:4,6-di-O-isopropylidene-D -allopyranose from D -glucose AnaM.Go ´mez, * Marı ´a D. Company, Attila Agocs, Clara Uriel, Serafı ´n Valverde and J. Cristo ´balLo ´pez * Instituto de Quı ´mica Orga ´nica General (CSIC), Juan de la Cierva 3, E-28006 Madrid, Spain Received 25 January 2005; received in revised form 12 April 2005; accepted 28 May 2005 Available online 23 June 2005 Abstract—2,3:4,6-Di-O-isopropylidene-D-allopyranosecanbeconvenientlypreparedfrom D-glucoseviaasyntheticsequence,which includes Mitsunobu inversion at O-3,di-O-isopropylidenation of phenyl-1-thio-D-allosideandanomericdeprotectionontreatment with NBS/CaCO 3 . Ó 2005 Elsevier Ltd. All rights reserved. Keywords: 2,3:4,6-Di-O-isopropylidene-D-allopyranose; Phenyl 1-thio-glycosides; NBS; Carbohydrate acetals Aspartofasyntheticprogramintendedfortheprepara- tion of carbasugars, 1–3 we have recently shown the usefulness of 2,3:4,6-di-O-isopropylidene acetals 1–3 of D-mannose, 2 D-glucose, 3 and D-galactose 3 as starting materials(Scheme1).Inthiscontext,wepublishedsome timeagoamethodfortheefficientpreparationof 2 and 3. 4 More recently, as a continuation of our research program, we required gram amounts of D-allose 2,3:4,6-di-O-isopropylidene acetal (4). In this Note, we discloseapracticalmethodforthepreparationof 4 from D-glucose. D-Allose (5) is a commercially available monosaccha- ride, however its high price 5 has activated the develop- ment of several methods for its preparation from inexpensive D-glucose. 6 On the other hand, whereas the kinetic acetonation of D-mannose, according to Gelas and Horton, 7,8 is the method of choice for the preparation of 1, similar acetonation of D-allose (5) led essentially exclusively (81%) to 4,6-O-isopropylid- ene-D-allopyranose (6) with only a minor amount (9%) of diacetonide 4. 8,9 A survey of the literature did not showanyadditionalprocedureforthepreparationof 4. Our strategy for the preparation of 4 (Scheme 2a) involved the synthesis of phenyl-1-thio-b-D-allopyrano- side 8, by Mitsunobu reaction of phenyl-1-thio-b-D- glucopyranoside 10, followed by deacetylation, 2,3:4,6- di-O-isopropylidene acetal formation and anomeric deprotection (8!9!4, Scheme 2a). Phenyl-1-thio-b-D- glucopyranose (10) was readily prepared, according to FerrierandFurneaux, 10 bytreatmentof b-D-glucopyra- nose pentaacetate 11 with boron trifluoride etherate and thiophenol. Mitsunobu reaction of methyl b-D-gluco- pyranoside with benzoic acid has been described by Weinges et al. to yield the corresponding 3,6-di-O-ben- zoyl-D-allopyranosederivativein87%yield. 6 Inthecase of the glucose derivative 10, this procedure gave poor yields of the corresponding allose dibenzoate. Alterna- tively, we have found that the use of acetic acid, rather than benzoic acid, triphenyl phosphine and diethyl azo- dicarboxylateyieldedphenyl-3,6-di-O-acetyl-1-thio-b-D- allopyranoside 7 in 82–84% yield (Scheme 2a). The crudeacetylesterwassaponifiedbythemethodofZem- plen 12a to yield phenyl-1-thio-b-D-allopyranoside (8), whichuponacetonationyieldedthioglycoside 9.Depro- tection of the anomeric thiophenyl protecting group on compound 9 was carried out by treatment with NBS in thepresenceofCaCO 3 toyieldthedesiredcompound 4 (J 1,2 =4.5Hz,CDCl 3 )in88%yield.Thiscompoundhas 0008-6215/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2005.05.011 * Corresponding authors. Tel.: +34 91 5622900; fax: +34 91 5644853 (A.M.G.), (J.C.L.);e-mail addresses: clopez@iqog.csic.es; anago@ iqog.csic.es; Carbohydrate RESEARCH Carbohydrate Research 340 (2005) 1872–1875