Septanoses and Derivatives

Despite the strong nucleophilicity of the thiol substituent, septanoses have not been found to spontaneously form from 6-thiosugars [5]. As with their namral counterparts, in cases where the formation of a pyranoid ring is not possible the 6-thiofuranose is favored over the 6-thioseptanose system [15,42]. 

Cox and Owen [42] and Whistler and Campbell [43] provided early synthetic approaches to the 6-thioseptanose system. The latter workers prepared a protected open-chain 6-thio dithioacetal of D-galactose that, upon deprotection at C-1 and S-6, could be cychzed to form the corresponding l,2,3,4,5-penta-0-acetyl-D-galacto-6-thioseptanose 37. From this intermediate, several derivatives, such as both anomers of the thioseptanosyl chloride as well as the methyl thioseptanosides, were synthesized. The methyl thioseptanoside was found to be more prone to hydrolysis than the corresponding sulfur containing pyranoid glycoside. 

6-Anhydroalditol derivatives such as 38 were recently obtained by Le Merrer from D-mannitol [34]. Following earlier results featuring antithrombotic properties of 1,5-dithiopyrano-sides, Kuszmann and coworkers [44] prepared a range of 1,6-dithioseptanosides. 

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Qualitative relaxation-studies have also been reported for an extensive series of derivatives of inositols, pentopyranoses, l,6-anhydro-/3-D-hexopyranoses, furanoses, and septanoses. In all instances, the experimentally determined Ri(ns) values reflect the anticipated geometry. For the furanose derivatives especially, they provide a better means for distinguishing between epimeric pairs than the relatively ambiguous interpretation of coupling-constant data. 

Even though the yields of the septanose derivatives in these reactions are decidedly modest, the products were isolated in sufficient quantities to permit analysis of their structures and conformations. Importantly, these routes provided enough of the respective septanoses to allow the preparation of alkylated and acylated glycoseptanosyl isomers. 

In addition to the major strategies previously outlined, other methods have also been utilized to synthesize septanosides. Among these, a bis-aldol addition of nitroalkanes onto pyranose-derived dialdehydes has been utilized to synthesize 3-nitro- and 4-nitro-septanosides.81-84 Such septanose derivatives are useful as they... 

We have observed intramolecular reactions of septanose species under a variety of reaction conditions using a number of starting materials. Figure 10 shows the putative reactive intermediates 190-193 that were present during iodoglycosidation of the D-xylose-derived oxepine 143, epoxidation of the oxepine 142, and TMS-triflate activation of septanosyl fluorides 72 and 75, respectively. Products 194-197 were obtained in a range of yields depending on whether or not other nucleophiles were present in the reaction. All of the intermediates are electrophilic and therefore... 

T. Q. Tran and J. D. Stevens, Septanose carbohydrates. VII. Preparation of mono-O-isopropylidene derivatives of methyl p-D-glucoseptanoside and preparation of methyl a-L-idoseptanoside and its derivatives, Aust. J. Chem., 55 (2002) 171-178. 

During the same study, the Italian researchers aiming at the synthesis of carbaoctanose compounds (vide infra), synthesized a nine-carbon long intermediate 308 which served both to access the octanose and the septanose targets. As shown in Scheme 50, the route to 308 entailed vinylogous aldol coupling between pyrrole 76 and D-arabinose derived aldehyde 306 producing lactam 307, the immediate precursor of 308. To... 

Only a few attempts at nucleophiHc substitution reactions with educts derived from (conformationally flexible) septanoses are known [76]. As can be seen from Table 10, besides straight Sn2, only elimination reactions have been reported [77]. Of interest is that in attempted substitutions of the epimeric 5-tosylates 103 and 105 (entries 1-3), the E[5,H-4] reaction (to give 104 containing a bridge head double bond) is preferred over the E[5,H-6] mode (which produces the glycal type 106) however, the latter product predominates when bulky bases (f-BuOK in f-BuOH, entry 4) are applied. 

The first report of the formation of a septanose could be traced back to the work of Micheel and Suckfiill in 1933 [7,8]. Pyranose derivative 1, upon treatment with acetic anhydride (AC2O), in the presence of pyridine, led to the formation of a/p-mixture of 6-deoxy per-O-acetyl-D-galactoseptanose 2 (Scheme 13.1a). Viability of the cyclization of acyclic precursors was reiterated further by Anet, and Stevens and coworkers for example, treatment of D-glucose with acetone in the presence of mineral acid afforded septanoside 3, although in yields less than 5% (Scheme 13.1b) [9,10]. 

The yields of the septanoside increased moderately when in i ltM-generated acyclic form underwent cyclization to the required derivative, as demonstrated by Gelas and coworkers [11]. Acid-sensitive isopropylidene and acetal functionalities in pyranoside derivative 4 facilitated pyranoside ring opening in the presence of pyridinium hydrochloride at 90°C and afforded the septanoside derivative 5, in a 43% yield (Scheme 13.2a). On the contrary, yield of septanose formation increased even further upon activation of the primary hydroxyl group as in aldohexose 6 with trityl-functionality, followed by treatment with Lewis acid to afford septanose 7 (Scheme 13.2b) [12]. 

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