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. 2022 Feb 16;27(4):1338.
doi: 10.3390/molecules27041338.

Synthesis of (+) -(R)-Tiruchanduramine

Zahraa S Al-Taie  1 , Barbara Bartholomew  2 , Christopher Cartmell  3 , Richard T Froom  4 , Russell G Kerr  3 , Rolf Kraehenbuehl  5 , Patrick J Murphy  4 , Robert J Nash  2 , Yana B Penkova  2 , Alexander van Teijlingen  4
Affiliations

Synthesis of (+) -(R)-Tiruchanduramine

Zahraa S Al-Taie et al. Molecules. .

Abstract

The absolute stereochemistry of the marine alkaloid (+)-(R)-tiruchanduramine was established via a convergent total synthesis in six steps and 15.5% overall yield from Fmoc-D-Dab(Boc)-OH.

Keywords: Synoicum macroglossum; guanidines; tiruchanduramine; β-carboline.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of tiruchanduramine (1).
Scheme 1
Scheme 1
Previously reported [1,2] racemic syntheses of 1: (a) DCC, DMAP, CH2Cl2, 62%, or (EDCI, HOBT, DMF) 65%. (b) (i) 2, CDI, THF:DMF (1:1); (ii) 5, NEt3, 1 week.
Scheme 2
Scheme 2
Conditions: (a) CDI, DMF, 30 min, then (S)-3, 24 h, 70%. (b) Boc2O (2.0 equiv.), NEt3 (2.0 equiv.), CH2Cl2, 16 h, 56%. (c) PPTSA (0.4 equiv.), MeOH, 71%. (d) DIAD or DEAD (2.4–6 equiv.), PPh3 (2.8–12 equiv.) THF or CH2Cl2, rt-reflux, 7 d.
Scheme 3
Scheme 3
Synthesis of (+)-(R)-1·HCO2H/HCl.(a) (i) EtOCOCl (1.1 equiv.), Et3N, THF; (ii) NaBH4 (3.0 equiv.), THF/H2O (1:1), −5 °C—rt, 3 h; 86%. (b) Piperidine:CH3Cl (1:4), 2 h. (c) 15 (1.5 equiv.), Et3N (3.0 equiv.), MeOH, rt, 2 d, 94%. (d) Imidazole (3.5 equiv.), dppe (1.5 equiv.), I2 (1.5 equiv.), CH2Cl2, −40 °C to −20 °C, 3 h. (e) HCl (aq 3M) 0 °C–rt, 48 h, (f) (i) 2 (1.03 equiv.), CDI (1.45 equiv), Et3N (3.0 equiv.), DMF, rt, 24 h, 18% (over three steps), (ii) HPLC.
Figure 2
Figure 2
Synthetic analogues of tiruchanduramine 1 (n = 4, 5) [14].
See this image and copyright information in PMC

References

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