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Synlett 2018; 29(20): 2669-2672
DOI: 10.1055/s-0037-1610326
DOI: 10.1055/s-0037-1610326
letter
The Total Synthesis of Spermine Alkaloid Kukoamine Bimesylate
Further Information
Publication History
Received: 14 June 2018
Accepted after revision: 23 October 2018
Publication Date:
14 November 2018 (online)
Abstract
The first total synthesis of kukoamine B bimesylate was completed from 1,4-diaminobutane dihydrochloride in 12 steps with a 11.4% overall yield, and all the steps could be carried out at a kilogram scale. The cyano groups were used as the precursor of amino groups to avoid the competitive reaction delicately. The aza-Michael addition reaction, amidation and hydrogenation of the cyano group sequence was streamlined as a general approach towards the synthesis of polyamine structures.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610326.
- Supporting Information
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References and Notes
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- 16 General Procedure To a solution of compound 1 (48.2 g, 0.04 mol) in THF (30 mL) was added methanol (700 mL) and methanesulfonic acid (5.9 mL, 0.09 mol). Then, palladium on carbon (4.8 g) was added to the mixture carefully. Air in the flask was exhausted, and the mixture was stirred at ambient temperature for 15 h under hydrogen atmosphere. TLC showed that all the starting materials were consumed (n-BuOH/H2O/HOAc = 4:1:1, UV), the mixture was filtered, and the was residue washed with THF. The filtrate was collected, and the solvent was removed in vacuum to give kukoamine B bimesylate (16.1 g, 73%) as white solid. 1H NMR (400 MHz, D2O): δ = 6.84–6.80 (m, 2 H), 6.75 (m, 2 H), 6.67–6.66 (m, 2 H), 3.39–3.34 (m, 2 H), 3.27–3.15 (m, 4 H), 2.91–2.79 (m, 2 H), 2.79 (m, 4 H), 2.79 (s, 6 H), 2.75–2.71 (m, 2 H), 2.66 (m, 2 H), 2.53 (m, 4 H), 1.82 (t, J = 6.8Hz, 2 H), 1.69 (t, J = 6.8 Hz, 2 H), 1.46 (m, 2 H), 1.34 (m, 2 H). 13C NMR (100 MHz, D2O): δ = 178.5, 178.3, 146.2, 146.1, 144.6, 135.8, 135.6, 135.2, 123.1, 123.0, 118.7, 118.5, 118.4, 49.9, 49.4, 46.8, 44.9, 40.7, 39.1, 39.0, 37.8, 36.3, 33.0, 32.7, 27.8, 27.3, 27.2, 25.1. ESI-HRMS: m/z calcd for C28H42N4O6 + H: 531.3183; found: 531.3185.