Concise and Enantioselective Synthesis of the Aminocyclitol Core of Hygromycin A

Abstract

[reaction: see text] Stereoselective aminohydroxylation and dihydroxylation using osmium(VIII) oxidants enabled the short and efficient synthesis of the aminocyclitol core of hygromycin A. In addition to allowing the selective introduction of the heteroatoms N and O, the use of osmium (via an osmate ester) as a protecting group for a 1,2-glycol is also reported. This tactic allowed efficient differentiation of otherwise equivalent hydroxyl groups and allowed us to complete the synthesis in short order (14 steps) and excellent overall yield (12%).

Structural, Functional and Calorimetric Investigation of MosA, a Dihydrodipicolinate Synthase from Sinorhizobium meliloti L5–30, does not Support Involvement in Rhizopine Biosynthesis

“…Synthetic methods have been developed for the preparation of aminocyclitols as these compounds are crucial components of many antibiotics [21,22] and potential lead compounds for glycosidase inhibitors, [23] but when we began our work the preparation of 1 had not been reported for 40 years. Early syntheses of 1 suffer from poor yields and the need to separate stereoisomers of the aminocyclitol.…”

Applications of Mitsunobu Reaction in total synthesis of natural products

“…The latter was subjected into classical Mitsunobu reaction to afford hydroxycyclohexenone p ‐nitrobenzoate 159 with the right configuration at the three stereogenic centers. Mitsunobu inversion at protected ‐OH group of 158 was required to obtain same configuration present in antroquinonols . Compound 159 was transformed into dimethyl ether 160 after several steps.…”

“…Mitsunobu inversion at protected -OH group of 158 was required to obtain same configuration present in antroquinonols. [217] Compound 159 was transformed into dimethyl ether 160 after several steps. The latter was underwent a-phenylselenylationselenoxide elimination to give the antroquinonol-type dimethylated cyclohexenoid core 161a.…”

Natural product synthesis as a challenging test of newly developed methodology

“…Our original construction of the core utilised 1st generation TA conditions (Scheme 20). 62 Our synthesis started from commercially available diketone 73, which was converted to mono-acetate 74 in two steps, with 98% ee, following the procedure of Ogasawara. 63 Mitsunobu inversion and ester hydrolysis furnished trans-diol 75.…”