Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 26;24(33):6202-6207.
doi: 10.1021/acs.orglett.2c02496. Epub 2022 Aug 11.

Ring Opening of Aziridines by Pendant Silanols Allows for Preparations of (±)-Clavaminol H, (±)-Des-Acetyl-Clavaminol H, (±)-Dihydrosphingosine, and (±)- N-Hexanoyldihydrosphingosine

Someshwar Nagamalla  1 , Debobrata Paul  1 , Joel T Mague  2 , Shyam Sathyamoorthi  1
Affiliations

Ring Opening of Aziridines by Pendant Silanols Allows for Preparations of (±)-Clavaminol H, (±)-Des-Acetyl-Clavaminol H, (±)-Dihydrosphingosine, and (±)- N-Hexanoyldihydrosphingosine

Someshwar Nagamalla et al. Org Lett. .

Abstract

We present a unique strategy for the synthesis of vicinal amino alcohols. Ring opening of aziridines with pendant silanols is compatible with a range of substrates. To engage productively in ring opening, the aziridine must be at least mildly activated, and a variety of such N-substituents are tolerated. The utility of this methodology is highlighted in facile preparations of the natural products (±)-Clavaminol H, (±)-dihydrosphingosine, and (±)-N-hexanoyldihydrosphingosine as well as a natural product analogue (±)-des-acetyl-Clavaminol H.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Approaches to Syntheses of vic-Amino Alcohols Juxtaposed with Our Work
Scheme 2.
Scheme 2.
Aziridine Silanols Can Be Prepared from (A) Alkenyl Silanols and (B) Aziridine Alcohols
Scheme 3.
Scheme 3.
Reaction Optimization aYield estimated from 1H NMR Integration with 4-nltrotoluene as an internal standard. b(R)-(−)-1,1′-Binaphthyl-2,2′-diyl hydrogen phosphate, arbitrarily chosen.
Scheme 4.
Scheme 4.
Effect of the Aziridine N-Substituent aCyciization was also attempted with (R)-BINOL Phosphoric Acid, and starting material was recovered. bAc = Acetyl; Ts = Tosyl; Cbz = benzyloxycarbonyl. aCCDC: 2177671.
Scheme 5.
Scheme 5.
Substrate Scope aProtocol A. bProtocol B. cProtocol A but with 30 mol % Ph3C+BF4− and reaction time of 12 h
Scheme 6.
Scheme 6.
Assembly of Some Natural Amino Alcohols
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Hayakawa Y; Rovero S; Forni G; Smyth MJ α-Galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis. Proc. Natl. Acad. Sci. U. S. A 2003, 100, 9464–9469. - PMC - PubMed
    1. Olivier NB; Altman RB; Noeske J; Basarab GS; Code E; Ferguson AD; Gao N; Huang J; Juette MF; Livchak S; Miller MD; Prince DB; Cate JHD; Buurman ET; Blanchard SC Negamycin induces translational stalling and miscoding by binding to the small subunit head domain of the Escherichia coli ribosome. Proc. Natl. Acad. Sci. U. S. A 2014, 111, 16274–16279. - PMC - PubMed
    1. Lacône V; Hunault J; Pipelier M; Blot V; Lecourt T; Rocher J; Turcot-Dubois A-L; Marionneau S; Douillard J-Y; Clément M; Le Pendu J; Bonneville M; Micouin L; Dubreuil D Focus on the Controversial Activation of Human iNKT Cells by 4-Deoxy Analogue of KRN7000. J. Med. Chem 2009, 52, 4960–4963. - PubMed
    1. Bergmeier SC The Synthesis of Vicinal Amino Alcohols. Tetrahedron 2000, 56, 2561–2576.
    1. Karjalainen OK; Koskinen AMP Diastereoselective synthesis of vicinal amino alcohols. Org. Biomol. Chem 2012, 10, 4311–4326. - PubMed

Publication types