Synthesis of chiral aminocyclitols via epoxyepimination

Braun, Heinz; Bürger, W.; Kresze, G.; Schmidtchen, Franz P.; Vaerman, Jean-Pierre; Viehe, H. G.

doi:10.1016/0957-4166(90)90041-8

Cited by 30 publications

(2 citation statements)

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“…Aminocyclitol derivatives are also found to be inhibitors of glycosidases and cell growth . Several strategies, − including chemo-enzymatic approach, SmI 2 -mediated pinacol-type coupling, and intramolecular NHC-catalyzed benzoin-type condensation, are available for the construction of aminocyclitol frameworks. Interestingly, McMurry coupling of a suitably substituted acyclic dialdehyde, wherein carbocyclization accompanied by installation of two of the hydroxyl groups of aminocyclitols, has never been investigated.…”

Section: Introductionmentioning

confidence: 99%

A Chiron Approach to Diversity-Oriented Synthesis of Aminocyclitols, (−)-Conduramine F-4 and Polyhydroxyaminoazepanes from a Common Precursor

Harit

Ramesh

2016

J. Org. Chem.

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The total syntheses of aminocyclitols, (-)-conduramine F-4, and polyhydroxyaminoazepanes have been achieved from a common precursor derived from tri-O-benzyl-d-glucal through a 'diversity-oriented' approach. Tri-O-benzyl-d-glucal was converted into a protected 1,6-diol through a sequence of steps that include transformation to a 2-tosylamidoglucose derivative, selective deprotection of primary C-6 benzyloxy group, LiAlH-mediated one-step reduction of acetate groups, and reductive ring opening of the resulting hemiacetal as the key steps. The 1,6-diol served as a common precursor in our diversity oriented approach toward the target molecules. Mesylation of the diol followed by double nucleophilic substitution reaction with primary amines led to the synthesis of amino-substituted polyhydroxyazepanes. On the other hand, dialdehyde obtained from the oxidation of 1,6-diol was found to be a convenient starting material for the synthesis of aminocyclitols and (-)-conduramine F-4. McMurry coupling of the dialdehyde was successfully employed, for the first time, to construct the carbocyclic framework of aminoyclitols, while bis-Wittig olefination of the dialdehyde followed by Grubb's(II)-catalyzed RCM delivered (-)-conduramine F-4. The stereochemistry of newly created chiral centers in aminocyclitols was established through single crystal X-ray crystallography and detailed NOE studies.

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Section: Introductionmentioning

confidence: 99%

A Chiron Approach to Diversity-Oriented Synthesis of Aminocyclitols, (−)-Conduramine F-4 and Polyhydroxyaminoazepanes from a Common Precursor

Harit

Ramesh

2016

J. Org. Chem.

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“…69,70 Some conduramines have activity as glycosidase inhibitors, 71 and these molecules provide access to many other biologically useful compounds including azasugars 72 and aminocyclitols. 73,74 Two examples of conduramine derivatives with medical relevance are Tamiflu ® (60) and N-octyl valienamine (61). Tamiflu ( 60) is a well-known aminocyclitol that is used for the treatment of influenza.…”

Section: Protein Folding and Pharmacological Chaperonesmentioning

confidence: 99%

Synthesis of small molecule inhibitors for the treatment of disease

Corkran¹

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<p>Three aspects of the protecting-group-free (PGF) synthesis of small molecules have been described in this thesis. In the first part, the PGF azasugar synthesis methodology was applied to 2-deoxy-D-glucose with the intention of selectively forming the six-membered azasugar 5-epi-fagomine. Surprisingly, four products were formed in the key I2-mediated carbamate annulation step, with a pyrrolidine being the major product after optimisation. This was formed in 15% yield. A mechanism that explains the formation of the four carbamates was proposed, which was supported by an investigation into related halocyclisation reactions. The next part of this thesis describes the development of a new PGF methodology for the synthesis of conduramines, another class of biologically interesting molecules. Conduramines are amino polyhydroxy cyclohexenes and some conduramines have glycosidase inhibitory activity. These molecules are also useful precursors to a variety of biologically useful molecules including aminocyclitols and azasugars. The key steps in the PGF synthesis of conduramines are a Vasella-Barbier amination, a reaction that forms new C-C and C-N bonds concomitantly, and a ring closing metathesis in the presence of free hydroxyl and amine groups. To this end, a 4-deoxy 3-conduramine was prepared in just four steps and in 27% yield. Finally, the preparation of an amine library and its biological testing for the identification of a new anti-tuberculosis drug is described. Two short syntheses were used to prepare alkenylamines and amines from the corresponding sugar, with various lipophilic groups attached to the amine. A 20-member amine library was prepared, and the compounds were tested for anti-mycobacterial activity in a mycobacterial growth inhibition assay. The most active compounds were subjected to further biological testing to determine their general cytotoxic properties. Two amines, arabinohexadecylamine and arabinohexadecylmethylamine, were identified as having the best potential for use as anti-tuberculosis drugs, and have been sent to Colorado State University for subsequent in vivo testing in a mouse model of tuberculosis.</p>

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