The absolute stereochemical assignment of SCH 71450, a selective dopamine D4 receptor antagonist, has been successfully confirmed through enantioselective epimer synthesis. An allyl substituent on the p‐hydroxybenzyl group was demonstrated to be an appropriate protecting group for Noyori Ru‐catalyzed asymmetric transfer hydrogenation of the imine derivative. The construction of the sugar moiety involved a β‐glycosylation reaction assisted by neighboring group participation. By comparison with literature data, the absolute stereochemistry at the C‐1 carbon on the tetrahydroisoquinoline core has been assigned the S configuration.
A practical method for the synthesis of 3-deoxy-L-ketohexoses is described. Both D- and L-ketohexoses can be transformed into rare 3-deoxy-L-ketohexoses in six steps through a group transfer process. The key step involves a radical cyclized onto a carbonyl group, followed by a fragmentation reaction, eventually resulting in the group transfer of an α-oxy carbonyl group. The process involves tin-free and environmentally benign radical conditions (TTMSS/AIBN/toluene). The acyclic form of 3-deoxy-L-fructose was prepared in only three steps from the inexpensive starting material, D-fructose. A further modification by preparing a dithioacetal derivative was accomplished, which could serve as a convenient sugar synthon for further synthetic applications. Removal of the dithioacetal protecting group results in the formation of the rare 3-deoxy-L-fructose in a total yield of 42%. This methodology could be further extended to the synthesis of other deoxy-L-ketohesoses, such as 3-deoxy-L-sorbose.
Two rare sugars – 1‐deoxy‐L‐fructose and L‐sorbose – were synthesized from inexpensive starting materials by a carbonyl translocation method developed in our laboratory. Reduction of a known starting compound gave a 1,5‐diol derivative. Selective protection of the corresponding primary alcohol and oxidation of the secondary alcohol provided the desired product in acyclic, protected form. Subsequent deprotection resulted in the production of 1‐deoxy‐L‐fructose from the known starting material in five steps and in a total yield of 42 %. This approach represents the first report of a chemical synthesis of 1‐deoxy‐L‐fructose. A similar strategy was applied to convert inexpensive D‐glucose into L‐sorbose, which was prepared in five steps from a known starting material in a total yield of 55 %. The synthetic methods represent a complementary method to biological approaches for the synthesis of vitamin C.
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