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
. 2010 Nov 8;12(6):850-4.
doi: 10.1021/cc1001023. Epub 2010 Sep 29.

S(N)Ar-based, facile synthesis of a library of benzothiaoxazepine-1,1'-dioxides

Alan Rolfe  1 , Thiwanka B Samarakoon, Sarra V Klimberg, Marek Brzozowski, Benjamin Neuenswander, Gerald H Lushington, Paul R Hanson
Affiliations

S(N)Ar-based, facile synthesis of a library of benzothiaoxazepine-1,1'-dioxides

Alan Rolfe et al. J Comb Chem. .

Abstract

The construction of a library of benzothiaoxazepine-1,1'-dioxides utilizing a one-pot, S(N)Ar diversification-ODCT(50) scavenging protocol is reported. This protocol combines microwave irradiation to facilitate the reaction, in conjunction with a soluble ROMP-derived scavenger (ODCT) to afford the desired products in good overall purity. Utilizing this protocol, a 78-member library was successfully synthesized and submitted for biological evaluation.

PubMed Disclaimer

Figures

Figure 3
Figure 3
Phenols, amines and sulfonamide nucleophiles for library synthesis.
Scheme 1
Scheme 1
One-pot epoxide cascade protocol library plan.
Scheme 2
Scheme 2
Synthesis of core benzothiaoxazepine-1,1’-dioxide scaffolds 1-9b.
Scheme 3
Scheme 3
Optimization of SNAr of phenol {6} on scaffold 1.
Scheme 4
Scheme 4
Optimization and utilization of ODCT as an efficient scavenger of phenol {6}.
Scheme 5
Scheme 5
Synthesis of the corresponding prototype library from scaffold 1 and 7.
Scheme 6
Scheme 6
Proposed 72-membered library of Benzothiaoxazepine-1,1’-dioxides.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. For reviews concerning ROMP reagents, see: Barrett AGM, Hopkins BT, Köbberling J. Chem Rev. 2002;102:3301–3324.. Flynn DL, Hanson PR, Berk SC, Makara GM. Curr Opin Drug Discovery Dev. 2002;5:571–579.. Harned AM, Probst DA, Hanson PR. The Use of Olefin Metathesis in Combinatorial Chemistry: Supported and Chromatography-Free Syntheses. In: Grubbs RH, editor. Handbook of Metathesis. Wiley-VCH; Weinheim, Germany: 2003. pp. 361–402.. Harned AM, Zhang M, Vedantham P, Mukherjee S, Herpel RH, Flynn DL, Hanson PR. Aldrichim Acta. 2005;38:3–16.

    1. Nicolaou KC, Chen JS. Chem Soc Rev. 2009;11:2993–3009. - PMC - PubMed
    2. Enders D, Grondal C, Hüttl MRM. Angew Chem Int Ed. 2007;46:1570–1581. - PubMed
    3. Tietze LF, Beifuss U. Angew Chem Int Ed Engl. 1993;32:131–163.
    4. Tietze LF, Brasche G, Gericke KM, editors. Wiley-VCH; Weinheim, Germany: 2006.
    5. Rolfe A, Young K, Hanson PR. Eur J Org Chem. 2008:5254–5262. - PMC - PubMed
    1. Drews J. Science. 2000;287:1960–1964. - PubMed
    2. Scozzafaa A, Owa T, Mastrolorenzo A, Supuran CT. Curr Med Chem. 2003;10:925–953. - PubMed
    1. Zhuang L, Wai JS, Embrey MW, Fisher TE, Egbertson MS, Payne LS, Guare JP, Jr, Vacca JP, Hazuda DJ, Felock PJ, Wolfe AL, Stillmock KA, Witmer MV, Moyer G, Schleif WA, Gabryelski LJ, Leonard YM, Lynch JJ, Jr, Michelson SR, Young SD. J Med Chem. 2003;46:453–456. - PubMed
    1. Levy L. Drugs Future. 1992;17:451–454.

Publication types

MeSH terms