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
. 2015 Jun 1;6(6):3599-3605.
doi: 10.1039/c5sc00338e. Epub 2015 May 5.

Enantioselective and diastereoselective azo-coupling/iminium-cyclizations: a unified strategy for the total syntheses of (-)-psychotriasine and (+)-pestalazine B

Qi Li  1   2 , Tingting Xia  2 , Licheng Yao  2 , Haiteng Deng  3 , Xuebin Liao  2
Affiliations

Enantioselective and diastereoselective azo-coupling/iminium-cyclizations: a unified strategy for the total syntheses of (-)-psychotriasine and (+)-pestalazine B

Qi Li et al. Chem Sci. .

Abstract

We report a unified strategy for the total syntheses of (-)-psychotriasine and (+)-pestalazine B based on the advanced intermediates of 3α-amino-hexahydropyrrolo[2,3-b]indole. To construct these structural motifs, a cascade reaction involving a BINOL-derived phosphoric anion-paired catalyst for enantioselective or diastereoselective azo-coupling/iminium-cyclizations was developed. The remaining key steps of the synthesis involve a sterically hindered amination via hypervalent iodine reagents and the Larock annulation. These transformations enable a general approach to the syntheses of indole alkaloids containing a 3α-amino-hexahydropyrrolo[2,3-b]indole motif and could be further applied to build a natural product-based library.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1. Compounds containing the 3α-amino-hexahydropyrrolo[2,3-b]indole core.
Fig. 2
Fig. 2. Reported synthetic methods for the 3α-amino-hexahydropyrrolo[2,3-b]indole core structure (a–e) and our approach in this publication and others (f).
Scheme 1
Scheme 1. Enantioselective azo-coupling of tryptamine derivatives.
Scheme 2
Scheme 2. Retrosynthetic analysis of (–)-psychotriasine (2).
Scheme 3
Scheme 3. Total synthesis of (–)-psychotriasine (2). Reagents and conditions: (a) (i) NaHMDS, Boc2O, THF, –60 °C; (ii) RANEY® nickel, hydrazine hydrate, MeOH, sealed tube, 70 °C, 88% yield over 2 steps; (b). Pd(OAc)2 (0.2 equiv.), xantphos (0.3 equiv.), t-BuONa (2.0 equiv.), toluene, 80 °C, 71% yield; (c) 13, Pd(OAc)2 (0.2 equiv.), DtBPF (0.3 equiv.), K2CO3 (2.5 equiv.), NMP, 110 °C, 83% yield; (d) (i) DIBAL-H (3.0 equiv.), toluene, –78 °C; (ii). ClCO2Me (3.0 equiv.), Na2CO3 (3.0 equiv.), DCM–H2O (2 : 1 ratio), rt, 64% yield over 2 steps; (e) (i) CF3CO2H, DCM, 0 °C; (ii) Red-Al (12.0 equiv.), toluene, reflux, 51% yield over 2 steps. Alkyne 13: N-(methoxycarbonyl)-4-(trimethylsilyl)-3-butynylamine.
Fig. 3
Fig. 3. Thermal ellipsoid plot of the X-ray structure of compound 16 at the 50% probability level.
Scheme 4
Scheme 4. Total synthesis of (+)-pestalazine B (4). Reagents and conditions: (a) PhN2BF4, K2CO3, CPA8a, DCE–THF (1.5 : 1), 0 °C, 79% yield; (b) hydrazine hydrate, Pd/C, EtOH, 85 °C, 80% yield; (c) A3, Cu(OTf)2, Na2CO3, DMF, 65 °C, 45% yield, (d) 21, Pd(OAc)2, DtBPF, Na2CO3, NMP, 80 °C, 57% yield.
See this image and copyright information in PMC

References

    1. Ruiz-Sanchis P., Savina S. A., Albericio F., Alvarez M. Chem.–Eur. J. 2011;17:1388. - PubMed
    1. Takayama H., Mori I., Kitajima M., Aimi N., Lajis N. H. Org. Lett. 2004;6:2945. - PubMed

    1. Leading studies on total synthesis of psychotrimine:

    2. Matsuda Y., Kitajima M., Takayama H. Org. Lett. 2008;10:125. - PubMed
    3. Newhouse T., Baran P. S. J. Am. Chem. Soc. 2008;130:10886. - PubMed
    4. Takahashi N., Ito T., Matsuda Y., Kogure N., Kitajima M., Takayama H. Chem. Commun. 2010;46:2501. - PubMed
    5. Newhouse T., Lewis C. A., Eastman K. J., Baran P. S. J. Am. Chem. Soc. 2010;132:7119. - PMC - PubMed
    6. Araki T., Ozawa T., Yokoe H., Kanematsu M., Yoshida M., Shishido K. Org. Lett. 2013;15:200. - PubMed
    7. Zhang H., Kang H., Hong L., Dong W., Li G., Zheng X., Wang R. Org. Lett. 2014;16:2394. - PubMed
    1. Schallenberger M. A., Newhouse T., Baran P. S., Romesberg F. E. J. Antibiot. 2010;63:685. - PMC - PubMed
    1. Waksman S. A., Bugie E. J. Bacteriol. 1944;48:527. - PMC - PubMed
    2. Mcinnes A. G., Taylor A., Walter J. A. J. Am. Chem. Soc. 1976;98:6741. - PubMed
    3. Kung A. L., Zabludoff S. D., France D. S., Freedman S. J., Tanner E. A., Vieira A., Cornell-Kennon S., Lee J., Wang B. Q., Wang J. M., Memmert K., Naegeli H. U., Petersen F., Eck M. J., Bair K. W., Wood A. W., Livingston D. M. Cancer Cell. 2004;6:33. - PubMed
    4. Cook K. M., Hilton S. T., Mecinovic J., Motherwell W. B., Figg W. D., Schofield C. J. J. Biol. Chem. 2009;284:26831. - PMC - PubMed
    5. Welch T. R., Williams R. M. Tetrahedron. 2013;69:770. - PMC - PubMed