b-Mannosidase and b-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxyvalienamine from D-mannose

Clinton Ramstadius; Omid Hekmat; Lars Eriksson; Henrik Stålbrand; Ian Cumpstey

doi:10.1016/j.tetasy.2009.02.016

b-Mannosidase and b-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxyvalienamine from D-mannose

Clinton Ramstadius, Omid Hekmat, Lars Eriksson, Henrik Stålbrand, Ian Cumpstey

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

18 Citationer (Scopus)

Abstract

A partially protected C-5@C-5a unsaturated carbasugar with a-lyxo configuration is synthesised in five
steps and 26% overall yield from a known mannose-derived hemiacetal, using ring-closing metathesis
as a key step. This carbasugar is converted into valienamine derivatives with b-lyxo (i.e., corresponding
to b-manno at C-1–C-4), a-lyxo (i.e., corresponding to a-manno at C-1–C-4) and b-2-acetamido-2-
deoxy-xylo (i.e., corresponding to b-GlcNAc at C-1–C-4) configurations. This is the first report of the synthesis
of the b-lyxo compound, 1,2-bis-epi-valienamine, which was found to inhibit Cellulomonas fimi bmannosidase
(CfMan2A) with Ki 140 lM. We report the crystal structures of three protected C-5@C-5a
unsaturated carbasugars with lyxo configuration.

Originalsprog	Engelsk
Tidsskrift	Tetrahedron: Asymmetry
Vol/bind	20
Udgave nummer	6-8
Sider (fra-til)	795-807
Antal sider	13
ISSN	0957-4166
DOI	https://doi.org/10.1016/j.tetasy.2009.02.016
Status	Udgivet - 7 maj 2009
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/j.tetasy.2009.02.016

Citationsformater

b-Mannosidase and b-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxyvalienamine from D-mannose. / Ramstadius, Clinton; Hekmat, Omid; Eriksson, Lars; Stålbrand, Henrik; Cumpstey, Ian.

I: Tetrahedron: Asymmetry, Bind 20, Nr. 6-8, 07.05.2009, s. 795-807.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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title = "b-Mannosidase and b-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxyvalienamine from D-mannose",

abstract = "A partially protected C-5@C-5a unsaturated carbasugar with a-lyxo configuration is synthesised in fivesteps and 26% overall yield from a known mannose-derived hemiacetal, using ring-closing metathesisas a key step. This carbasugar is converted into valienamine derivatives with b-lyxo (i.e., correspondingto b-manno at C-1–C-4), a-lyxo (i.e., corresponding to a-manno at C-1–C-4) and b-2-acetamido-2-deoxy-xylo (i.e., corresponding to b-GlcNAc at C-1–C-4) configurations. This is the first report of the synthesisof the b-lyxo compound, 1,2-bis-epi-valienamine, which was found to inhibit Cellulomonas fimi bmannosidase(CfMan2A) with Ki 140 lM. We report the crystal structures of three protected C-5@C-5aunsaturated carbasugars with lyxo configuration.",

author = "Clinton Ramstadius and Omid Hekmat and Lars Eriksson and Henrik St{\aa}lbrand and Ian Cumpstey",

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T1 - b-Mannosidase and b-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxyvalienamine from D-mannose

AU - Ramstadius, Clinton

AU - Hekmat, Omid

AU - Eriksson, Lars

AU - Stålbrand, Henrik

AU - Cumpstey, Ian

PY - 2009/5/7

Y1 - 2009/5/7

N2 - A partially protected C-5@C-5a unsaturated carbasugar with a-lyxo configuration is synthesised in fivesteps and 26% overall yield from a known mannose-derived hemiacetal, using ring-closing metathesisas a key step. This carbasugar is converted into valienamine derivatives with b-lyxo (i.e., correspondingto b-manno at C-1–C-4), a-lyxo (i.e., corresponding to a-manno at C-1–C-4) and b-2-acetamido-2-deoxy-xylo (i.e., corresponding to b-GlcNAc at C-1–C-4) configurations. This is the first report of the synthesisof the b-lyxo compound, 1,2-bis-epi-valienamine, which was found to inhibit Cellulomonas fimi bmannosidase(CfMan2A) with Ki 140 lM. We report the crystal structures of three protected C-5@C-5aunsaturated carbasugars with lyxo configuration.

AB - A partially protected C-5@C-5a unsaturated carbasugar with a-lyxo configuration is synthesised in fivesteps and 26% overall yield from a known mannose-derived hemiacetal, using ring-closing metathesisas a key step. This carbasugar is converted into valienamine derivatives with b-lyxo (i.e., correspondingto b-manno at C-1–C-4), a-lyxo (i.e., corresponding to a-manno at C-1–C-4) and b-2-acetamido-2-deoxy-xylo (i.e., corresponding to b-GlcNAc at C-1–C-4) configurations. This is the first report of the synthesisof the b-lyxo compound, 1,2-bis-epi-valienamine, which was found to inhibit Cellulomonas fimi bmannosidase(CfMan2A) with Ki 140 lM. We report the crystal structures of three protected C-5@C-5aunsaturated carbasugars with lyxo configuration.

U2 - 10.1016/j.tetasy.2009.02.016

DO - 10.1016/j.tetasy.2009.02.016

M3 - Journal article

VL - 20

SP - 795

EP - 807

JO - Tetrahedron Asymmetry

JF - Tetrahedron Asymmetry

SN - 0957-4166

IS - 6-8

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