Prearranged Glycosides, Part 12, Intramolecular Mannosylations of ...

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2660 Helvetica Chimica Acta ± Vol. 83 2000) The two prearranged glycosides tethered with a malonate spacer via position 6 of the mannosyl donor to position 2 and 6, respectively, of the glucosyl acceptor were prepared from ethyl 1-thiomannoside 34 [41]. Thus, condensation of the latter with benzyl 3-O-benzoyl-4,6-O-benzylidene-a-d-glucopyranoside 35) [52], followed by regioselective opening of the benzylidene group of intermediate 36, afforded the prearranged glycoside 37 Scheme 4). Cyclization of compound 37 gave exclusively the tethered a-d-linked disaccharide 38 see below, Table), which was deacylated and benzoylated to afford 39 in 73% yield. Both disaccharides showed C,H-coupling constants typical for an a-d-linkage 1 J ˆ 168.8 38) and 171.8 Hz 39)). Similarly, 34 was condensed regioselectively with benzyl 2,3-di-O-benzoyl-a-d-glucopyranoside 40) [53] to give the prearranged glycoside 41 65%), cyclization of which see below, Table) and subsequent deacylation and benzoylation afforded a-d-linked disaccharides 42 and 43, respectively 1 J ˆ 172.542) and 172.0 Hz 43)). Scheme 4 Discussion. ±TheTable summarizes the results for the cyclizations of tethered disaccharides 5, 17, 23, 28, 31, 37, and 41. All cyclizations described here were performed in CH 2Cl 2 or MeCN with N-iodosuccinimide NIS) for phenyl and ethyl 1-thioglycosides and with methyl trifluoromethanesulfonate MeOTf) for ethyl 1-thioglycosides, as previously described [41]. The results of the cyclizations of prearranged glycosides 5 Table, Entries 1 ± 3) having the succinate tether at position 2 of the mannosyl donor and at position 3 of the glucosyl acceptor are in contrast to previously performed glycosylations with glucosyl or galactosyl instead of mannosyl donors [31] [39] [42]. In the case of 5, solely a-d-1 ! 4)-linked disaccharides were found. It was originally expected for compounds 5 to give at least significant amounts of the corresponding b-dlinked disaccharides. That this was not the case may be explained by the results of forcefield calculations [54] performed for the a-d-linked product 6 and its b-d-linked
counterpart and their comparison with those of galactosyl-derived analogues. For example, for disaccharides obtained from 1-thiogalactosides tethered via position 2 by succinate to position 3 of a glucose acceptor, the corresponding a-d-1 ! 4)-linked saccharides are ca. 7 ± 12 kcal/mol more stable than the respective b-d-1 ! 4)-linked ones [39]. Contrarily, compound 6 is calculated to be ca. 36 kcal/mol more stable than the corresponding b-d-linked disaccharide. Thus, solely 6 was formed in the cyclizations of prearranged saccharides 5. Table. Cyclization of Tethered Glycosides 5, 17, 23, 28, 31, and 41 under Various Conditions to Tethered 1! 4)-Linked Disaccharides Entry Starting material leaving group) Tether Man ! Glc) Tether linkage Ring size Conditions Products yield) a-d/b-d 1 5a PhS) succinate 2 ! 3) 11 NIS, CH2Cl2, 308 6 71%) 100 : 0 2 NIS, MeCN, 308 6 73%) 100 : 0 3 5b EtS) succinate 2 ! 3) 11 NIS, MeCN, 308 6 54%) a ) 100 : 0 4 17a PhS) succinate 3 ! 3) 12 NIS, CH2Cl2, 308 18a 17%), 18b 50%) 26 : 74 5 NIS, MeCN, 308 18a 12%), 18b 53%) 18 : 82 6 17b EtS) succinate 3 ! 3) 12 NIS, CH2Cl2, 308 18 64%) 10 : 90b ) 7 NIS, MeCN, 308 18a 0%), 18b 66%) 0 : 100 8 MeOTf, CH2Cl2, r.t. 18 64%) 17 : 83b ) 9 MeOTf, MeCN, r.t. 18a 64%), 18b 0%) 100 : 0 10 23 EtS) malonate 3 ! 3) 11 NIS, CH2Cl2, 308 c ) 11 MeOTf, CH2Cl2, r.t. c ) 12 28 PhS) succinate 4 ! 3) 12 NIS, CH2Cl2, 308 29a 73%), 29b 5%) 94 : 6 13 NIS, MeCN, 308 29a 69%), 29b 7%) 91 : 9 14 31a EtS) malonate 6 ! 3) 12 NIS, CH2Cl2, 308 32a 17%), 32b 53%) 24 : 76d ) 15 MeOTf, CH2Cl2, r.t. 32a 9%), 32b 68%) 12 : 88d ) 16 31b EtS) succinate 6 ! 3) 13 NIS, CH2Cl2, 308 33a 43%), 33b 27%) 62: 38d ) 17 MeOTf, CH2Cl2, r.t. 33a 31%), 33b 37%) 45: 55 d ) 18 31c PhS) succinate 6 ! 3) 13 NIS, CH2Cl2, 308 33a 53%), 33b 21%) 71 : 29d ) 19 37 EtS) malonate 6 ! 2) 13 NIS, CH2Cl2, 308 38 69%) 100 : 0 20 NIS, MeCN, 308 38 69%) 100 : 0 21 MeOTf, CH2Cl2, r.t. 38 68%) 100 : 0 22 MeOTf, MeCN, r.t. 38 71%) 100 : 0 23 41 EtS) malonate 6 ! 6) 13 NIS, CH2Cl2, 308 42 72%) 100 : 0 24 NIS, MeCN, 308 42 68%) 100 : 0 25 MeOTf, CH2Cl2, r.t. 42 62%) 100 : 0 26 MeOTf, MeCN, r.t. 42 66%) 100 : 0 a ) According to [34]. b ) Determined from the ratio 19a/19b. c ) Decomposition of the starting material. d ) According to [41]. Helvetica Chimica Acta ± Vol. 83 2000) 2661
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