Part 1. Dihydroisoxazole-based synthesis of 2-amino-2-deoxytetroses and 2,3,6-trideoxy-3-aminohexoses. Part 2. Synthetic studies directed towards the preparation of polynitrospiropentane derivatives

Stephen Girard D'Ambrosio

doi:10.17918/00000642

Part I. A diastereoselective route has been developed for the synthesis of racemic 2-amino-2-deoxythreose derivatives from dihydroisoxazole (DHI) intermediates. Nitro DHI 199 was derived from condensation of chloroacetaldehyde with nitromethane followed by protection and nitrosative cyclization. Replacement of the nitro group of 199 by dithiane and subsequent reductive cleavage furnished the open-chain diastereomeric amino alcohols 196a,b. A reproducible ratio of >90:10 196a/196b was obtained using freshly prepared LiBH4. The amino alcohols were converted to their corresponding amides 203a and 203b which were chromatographically separated. The major amide 203a was transformed to 2-amino-2-deoxythreose derivative 1a in 3% overall yield from 186. The minor amide 203b was transformed in analogous fashion to produce erythrose derivative 1b and its anomeric isomer 1c. Optically active 2-amino-2-deoxy-D-threose derivatives 1a and 227 have been prepared from D-glyceraldehyde acetonide (28). Strecker reaction of 28 with benzylamine and KCN gave a diastereomeric mixture of nitriles 63,69. Contrary to the literature, the reported separation of 69 from 63 and the selective hydrolysis of the acetonide group of 63 could not be accomplished. The nitrile diastereomers 63,69 were carried forward as a mixture to the amines 224,225 which were readily separable. The amine 224 was transformed in stepwise fashion to 2-amino-2-deoxythreose derivatives 1a and 227. The corresponding erythrose derivatives 1b and 232 were prepared similarly. A route for the synthesis of L-daunosamine derivative 2a in high optical purity has been developed utilizing the Sharpless catalytic AD reaction. Dihydroxylation of alkenyl DHI 222 with AD-mix-[alpha] furnished the diol 223 in 92% e.e.. Protection of 223 as the benzylidene acetal gave DHIs 234a,b from which 234a was obtained as the major isomer. Diastereoselective reductive ring-opening of DHI 234a with lithium borohydride provided amino alcohols 235a,b (235a/235b, 3:1) which were converted to their corresponding acetamides and chromatographically separated. The major isomer 236a was transformed to L-daunosamine derivative 2a ([alpha]23D = -210.2[degrees] (c = 1.18, chloroform)). The DHI 234b was similarly transformed into 2a. High diastereoselectivity was obtained for osmium catalyzed dihydroxylation of alkenyl DHI 271 and 272 either syn or anti to the allylic C-O bond. Catalytic AD reaction of 272 using (DHQD)2-PHAL as the chiral auxiliary (anti, matched pair) afforded the diol in 96% d.e. The other diastereomer predominated (90% d.e.) with (DHQ)2-PHAL as the chiral auxiliary (syn, mismatched pair). Similar results were obtained for the AD reaction of 271. Part II. Dinitro compound 302 was synthesized from ketone 300 via aldol and Michael reactions. Cyclization of 302 using sodium acetate/iodine afforded dinitrocyclopropane 305. The new cyclization approach also afforded trans-1,2-dinitrocyclopropane more efficiently than the former procedure employing dimsyl sodium/iodine.

Part 1. Dihydroisoxazole-based synthesis of 2-amino-2-deoxytetroses and 2,3,6-trideoxy-3-aminohexoses. Part 2. Synthetic studies directed towards the preparation of polynitrospiropentane derivatives

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Part 1. Dihydroisoxazole-based synthesis of 2-amino-2-deoxytetroses and 2,3,6-trideoxy-3-aminohexoses. Part 2. Synthetic studies directed towards the preparation of polynitrospiropentane derivatives

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