Differentially-protected steroidal triamines: scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry

Vicente Del Amo; Laura Siracusa; Theodoros Markidis; Beatriz Baragaña; Khadga M. Bhattarai; Marta Galobardes; Gregorio Naredo; M. Nieves Pérez-Payán; Anthony P. Davis

doi:10.1039/b412298d

Differentially-protected steroidal triamines: scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry

Vicente Del Amo
, Laura Siracusa
, Theodoros Markidis
, Beatriz Baragaña
, Khadga M. Bhattarai
, Marta Galobardes
, Gregorio Naredo
, M. Nieves Pérez-Payán
, Anthony P. Davis

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

53 Citations (Scopus)

Abstract

Cholic acid 2a has been converted into two new orthogonally-protected triamino scaffolds, 13 and 14. The synthesis proceeds via the bis-Boc-NH-substituted azide 10, for which an improved preparation is described. After removal of the Boc groups, the two axial amines are differentiated through a novel monoprotection employing 1-(2-nitrobenzenesulfonyloxy)-benzotriazole 29. Regioselectivity of ≥50:1 is achieved, presumably reflecting an exceptional sensitivity to steric hindrance. Protection of the remaining amino group as Boc or Alloc gives the scaffolds in ∼40% overall yield from cholic acid. Scaffold 13 has been sequentially deprotected and derivatised with N-carbamoyl amino acids, to give a model for tripodal peptide libraries.

Original language	English
Pages (from-to)	3320-3328
Number of pages	9
Journal	Organic and Biomolecular Chemistry
Volume	2
Issue number	22
DOIs	https://doi.org/10.1039/b412298d
Publication status	Published - 15 Oct 2004

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1039/b412298d

Cite this

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title = "Differentially-protected steroidal triamines: scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry",

abstract = "Cholic acid 2a has been converted into two new orthogonally-protected triamino scaffolds, 13 and 14. The synthesis proceeds via the bis-Boc-NH-substituted azide 10, for which an improved preparation is described. After removal of the Boc groups, the two axial amines are differentiated through a novel monoprotection employing 1-(2-nitrobenzenesulfonyloxy)-benzotriazole 29. Regioselectivity of ≥50:1 is achieved, presumably reflecting an exceptional sensitivity to steric hindrance. Protection of the remaining amino group as Boc or Alloc gives the scaffolds in ∼40\% overall yield from cholic acid. Scaffold 13 has been sequentially deprotected and derivatised with N-carbamoyl amino acids, to give a model for tripodal peptide libraries.",

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year = "2004",

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doi = "10.1039/b412298d",

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publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - Differentially-protected steroidal triamines

T2 - scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry

AU - Amo, Vicente Del

AU - Siracusa, Laura

AU - Markidis, Theodoros

AU - Baragaña, Beatriz

AU - Bhattarai, Khadga M.

AU - Galobardes, Marta

AU - Naredo, Gregorio

AU - Pérez-Payán, M. Nieves

AU - Davis, Anthony P.

PY - 2004/10/15

Y1 - 2004/10/15

N2 - Cholic acid 2a has been converted into two new orthogonally-protected triamino scaffolds, 13 and 14. The synthesis proceeds via the bis-Boc-NH-substituted azide 10, for which an improved preparation is described. After removal of the Boc groups, the two axial amines are differentiated through a novel monoprotection employing 1-(2-nitrobenzenesulfonyloxy)-benzotriazole 29. Regioselectivity of ≥50:1 is achieved, presumably reflecting an exceptional sensitivity to steric hindrance. Protection of the remaining amino group as Boc or Alloc gives the scaffolds in ∼40% overall yield from cholic acid. Scaffold 13 has been sequentially deprotected and derivatised with N-carbamoyl amino acids, to give a model for tripodal peptide libraries.

AB - Cholic acid 2a has been converted into two new orthogonally-protected triamino scaffolds, 13 and 14. The synthesis proceeds via the bis-Boc-NH-substituted azide 10, for which an improved preparation is described. After removal of the Boc groups, the two axial amines are differentiated through a novel monoprotection employing 1-(2-nitrobenzenesulfonyloxy)-benzotriazole 29. Regioselectivity of ≥50:1 is achieved, presumably reflecting an exceptional sensitivity to steric hindrance. Protection of the remaining amino group as Boc or Alloc gives the scaffolds in ∼40% overall yield from cholic acid. Scaffold 13 has been sequentially deprotected and derivatised with N-carbamoyl amino acids, to give a model for tripodal peptide libraries.

UR - https://www.scopus.com/pages/publications/10244256427

U2 - 10.1039/b412298d

DO - 10.1039/b412298d

M3 - Article

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AN - SCOPUS:10244256427

SN - 1477-0520

VL - 2

SP - 3320

EP - 3328

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 22

ER -

Differentially-protected steroidal triamines: scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry

Abstract

ASJC Scopus subject areas

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