Stereoselective Synthesis of Orthogonally Protected 1,2-Diaminoinositols from d-Mannose

Abstract

We present herein a promising novel strategy for the transformation of sugar aldehydes into 1,2-diaminoinositols. This process, based on the sequential intermolecular aza-Henry reaction and intermolecular Henry reaction allowed the total synthesis of a 1,2-diaminoinositols with total stereochemical control. The new route constitutes a simpler and more efficient approach than those previously described routes to 1,2-diaminoinositols and it has the additional advantage of offering the possibility of orthogonal protection of the amino groups.

Key words

Henry reaction - aza-Henry reaction - bromonitro­alkanes - 1,2-diaminoinositols - 2-nitroamines

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• 18 1-d-[1,4,5/2,3,6]-6-Benzyloxycarbonylamino-2,3-O-isopropylidene-5-(4-methoxyphenylamino)-1,4-di-O-triethylsilylcyclohexane-1,2,3,4-tetraol (10) [α]_D ²² +0.6 (c 0.2 in CDCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.31–7.25 (m, 5 H), 6.73 (app q, J = 8.5 Hz, 2 H), 6.50 (app q, J = 8.5 Hz, 2 H), 5.02 (s, 2 H), 4.49 (d, J = 9.0 Hz, 1 H), 4.33 (br s, 1 H), 4.15–4.06 (m, 2 H), 3.96–3.86 (m, 2 H), 4.15–4.06 (m, 2 H), 3.72 (s, 3 H), 3.69–3.55 (m, 2 H), 1.52 (s, 3 H), 1.37 (s, 3 H), 0.95–0.90 (m, 18 H), 0.66–0.55 (m, 12 H). ¹³C NMR (100 MHz, CDCl₃): δ = 157.1 (C), 151.8 (C), 141.77(C), 136.5 (C), 128.4 (2 × CH), 128.0 (2 × CH), 115.0 (2 × CH), 114.0 (2 × CH), 109.2 (C), 80.9 (CH), 77.7 (CH), 68.8 (CH), 66.2 (CH₂), 55.9 (CH), 55.8 (CH₃), 53.8 (CH), 28.4 (CH₃), 26.3 (CH₃), 6.8 (6 × CH₃), 5.0 (3 × CH₂), 4.8 (3 × CH₂). MS (ESI⁺): m/z (%) = 687 (100) [M + H]⁺. HRMS (ESI⁺): m/z calcd for C₃₆H₅₉N₂O₇Si₂ [M + H]⁺: 687.3843; found: 687.3855.