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The first preparative solution phase synthesis of melanotan II

Melanotan II is a synthetic cyclic heptapeptide used to prevent a sunlight-induced skin cancer by stimulating the skin tanning process. In this paper we report the first solution phase synthesis of the title compound. The hexapeptide sequence has been assembled by [(2+2)+1+1] scheme. After removing...

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Autores principales: Ryakhovsky, Vladimir V, Khachiyan, Georgy A, Kosovova, Nina F, Isamiddinova, Elena F, Ivanov, Andrey S
Formato: Texto
Lenguaje:English
Publicado: Beilstein-Institut 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587946/
https://www.ncbi.nlm.nih.gov/pubmed/19043625
http://dx.doi.org/10.3762/bjoc.4.39
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author Ryakhovsky, Vladimir V
Khachiyan, Georgy A
Kosovova, Nina F
Isamiddinova, Elena F
Ivanov, Andrey S
author_facet Ryakhovsky, Vladimir V
Khachiyan, Georgy A
Kosovova, Nina F
Isamiddinova, Elena F
Ivanov, Andrey S
author_sort Ryakhovsky, Vladimir V
collection PubMed
description Melanotan II is a synthetic cyclic heptapeptide used to prevent a sunlight-induced skin cancer by stimulating the skin tanning process. In this paper we report the first solution phase synthesis of the title compound. The hexapeptide sequence has been assembled by [(2+2)+1+1] scheme. After removing the orthogonal protection, a carbodiimide mediated lactamization, involving the ε-amino group of lysine and γ-carboxy group of aspartic acid, led to a cyclic intermediate. Appending N-acetylnorleucine concluded the assembly of melanotan II molecule. Protection of the lateral groups in arginine and tryptophan was omitted for atom and step economy reasons. The total synthesis of melanotan II was accomplished in 12 steps with 2.6% overall yield, affording >90% pure peptide without using preparative chromatography.
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spelling pubmed-25879462008-11-28 The first preparative solution phase synthesis of melanotan II Ryakhovsky, Vladimir V Khachiyan, Georgy A Kosovova, Nina F Isamiddinova, Elena F Ivanov, Andrey S Beilstein J Org Chem Full Research Paper Melanotan II is a synthetic cyclic heptapeptide used to prevent a sunlight-induced skin cancer by stimulating the skin tanning process. In this paper we report the first solution phase synthesis of the title compound. The hexapeptide sequence has been assembled by [(2+2)+1+1] scheme. After removing the orthogonal protection, a carbodiimide mediated lactamization, involving the ε-amino group of lysine and γ-carboxy group of aspartic acid, led to a cyclic intermediate. Appending N-acetylnorleucine concluded the assembly of melanotan II molecule. Protection of the lateral groups in arginine and tryptophan was omitted for atom and step economy reasons. The total synthesis of melanotan II was accomplished in 12 steps with 2.6% overall yield, affording >90% pure peptide without using preparative chromatography. Beilstein-Institut 2008-10-30 /pmc/articles/PMC2587946/ /pubmed/19043625 http://dx.doi.org/10.3762/bjoc.4.39 Text en Copyright © 2008, Ryakhovsky et al. https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Ryakhovsky, Vladimir V
Khachiyan, Georgy A
Kosovova, Nina F
Isamiddinova, Elena F
Ivanov, Andrey S
The first preparative solution phase synthesis of melanotan II
title The first preparative solution phase synthesis of melanotan II
title_full The first preparative solution phase synthesis of melanotan II
title_fullStr The first preparative solution phase synthesis of melanotan II
title_full_unstemmed The first preparative solution phase synthesis of melanotan II
title_short The first preparative solution phase synthesis of melanotan II
title_sort first preparative solution phase synthesis of melanotan ii
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587946/
https://www.ncbi.nlm.nih.gov/pubmed/19043625
http://dx.doi.org/10.3762/bjoc.4.39
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