Total Synthesis and Absolute Configuration of Minalemine A, a Guanidine Peptide from the Marine Tunicate Didemnum rodriguesi

Abstract

The total synthesis of the 3S,2S and 3R,2S diastereomers (1a and 1b) of minalemine A and the identification of the natural compound as the 3R,2S isomer is described. The key step in the synthesis is the preparation of the two enantiomers of the beta-amino diacid 3-(N-carboxymethyl)-aminodecanoic acid (Ncma), which were obtained by stereoselective alkylation with allyl bromide of two nonanoic acid imides bearing chiral oxazolidinones as chiral auxiliaries. Natural minalemine A shows identical 1H NMR and very similar 13C NMR spectra compared to the two synthetic diastereomers. Sufficient differences in their chromatographic behavior to allow conclusive identification were not found. However, the corresponding N-2-naphthoyl amides presented quite distinct circular dichroism spectra (CD), and these confirmed the 3R,2S configuration for the natural minalemines and the R configuration for the constituent beta-amino diacid, Ncma.

Efficient synthetic protocol for substituted guanidines via copper(I)-mediated intermolecular amination of isothiourea derivatives

“…Other solvents and other simple chemicals were purchased and used as such. S-methyl-N,N 0 -bis(tert-butoxycarbonyl)isothiourea (4) and N,N 0 -bis(tert-butoxycarbonyl)thiourea (7) were prepared according to the literature procedure [10,11], respectively.…”

Polymethyleneamine Alkaloids of Animal Origin: I. Metabolites of Marine and Microbial Organisms

“…Minalemines A-F (XLII)-(XLVII) were isolated from Didemnun rodriguesi. These interesting metabolites have an equal backbone and contain agmatine and homoagmatine fragments along with β-N-carboxymethyl derivatives of long-chain β-amino acids [30,31].…”

New Cyanopeptide‐Derived Low Molecular Weight Inhibitors of trypsin‐like Serine Proteases

“…Using the first route, the Boc protecting groups were introduced twice in thiourea by means of di-tert-butyl dicarbonate -upon deprotonation of thiourea by sodium hydride [14]. Bis-Boc-thiourea (9) was subjected to the nucleophilic attack of 1,4-diaminobutane to give the desired bis-Boc-agmatine (11) [15]. In a second route, S-methylisothiouronium sulfate was acylated by di-tert-butyl dicarbonate in a two-phase-mixture under alkaline conditions to the bis-Boc-substituted derivative 10 [16,17], which reacted with 1,4-diaminobutane to 11 [18].…”