Efficient Synthesis of a 5α-Reductase Inhibitor, 3-(Tetrazol-5-yl)-3,5-pregnadien-20-one through Allylic Rearrangement of Cyanophosphates

Hiroki Yoneyama; Yoshihide Usami; Shinya Harusawa

doi:10.1055/s-0037-1612060

Synthesis, Table of Contents

Synthesis 2019; 51(08): 1791-1794
DOI: 10.1055/s-0037-1612060

paper

Efficient Synthesis of a 5α-Reductase Inhibitor, 3-(Tetrazol-5-yl)-3,5-pregnadien-20-one through Allylic Rearrangement of Cyanophosphates

Hiroki Yoneyama

,

Yoshihide Usami

,

Shinya Harusawa*

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan Email: harusawa@gly.oups.ac.jp

› Author Affiliations

Abstract

All articles of this category

Abstract

We describe the use of allylic rearrangements of cyanophosphates for the efficient and practical synthesis of 3-(tetrazol-5-yl)-3,5-pregnadien-20-one, which is a potent 5α-reductase inhibitor (IC₅₀: 15.6 nM), from pregnene-3,20-dione in 92% overall yield in four steps.

Key words

synthesis - DEPC - cyanophosphates - allylic rearrangement - 3-(tetrazol-5-yl)-3,5-pregnadien-20-one - 5AR inhibitor

Full Text

References

References
1 Schmidt LJ, Tindall DJ. J. Steroid Biochem. Mol. Biol. 2011; 32
2 Andersson S, Russell DW. Proc. Natl. Acad. Sci. U.S.A. 1990; 87: 36402
3 Vaughan D, Imperato-McGinley J, McConnell J, Matsumoto AM, Bracken B, Roy J, Sullivan M, Pappas F, Cook T, Daurio C, Meehan A, Stoner E, Waldstreicher J. Urology 2002; 60: 1040
4 Bull HG, Garcia-Calvo M, Andersson S, Baginsky WF, Chan HK, Ellsworth DE, Miller RR, Stearns RA, Bakshi RK, Rasmusson GH, Tolman RL, Myers RW, Kozarich JW, Harris GS. J. Am. Chem. Soc. 1996; 118: 2359
5 Uygur MC, Gur E, Arik AI, Altud U, Erol D. Andrology 1998; 30: 5
6 Aggarwal S, Mahapatra MK, Kumar R, Bhardwaj TR, Hartmann RW, Haupenthal J, Kumar M. Bioorg. Med. Chem. 2016; 24: 779

7a Baine NH, Owings FF, Kline DN, Resnick T, Pig L.-J, Fox M, Mewshaw RE, Tickner AM, Kowalski CJ. J. Org. Chem. 1994; 59: 5987
7b Aggarwal S, Thareja S, Bhardwaj TR, Haupenthal J, Hartmann RW, Kumar M. Eur. J. Med. Chem. 2012; 54: 728
7c Lao K, Sun J, Wang C, Lyu W, Zhou B, Zhao R, Xu Q, You Q, Xiang H. Steroids 2017; 124: 29

8 Harusawa S, Yoneda R, Kurihara T, Hamada Y, Shioiri T. Tetrahedron Lett. 1984; 25: 427

For the recent reviews on DEPC and CPs, see:

9a Harusawa S, Shioiri T. Tetrahedron 2016; 72: 8125
9b Patel HH, Shioiri T. Encyclopedia of Reagents for Organic Synthesis, 2nd ed., Vol. 5. Paquette LA, Crich D, Fuchs PL, Molander GA. John Wiley & Sons; New York: 2009: 3737-3743

10a Harusawa S, Miki M, Yoneda R, Kurihara T. Chem. Pharm. Bull. 1985; 33: 2164
10b Kurihara T, Miki M, Yoneda R, Harusawa S. Chem. Pharm. Bull. 1986; 34: 2747
10c Kurihara T, Miki M, Santo K, Harusawa S, Yoneda R. Chem. Pharm. Bull. 1986; 34: 4620

11 In connection with this study, the reaction mechanism for the transformation of enone CPs into diene nitriles was reinvestigated (see Supporting Information)

12a Yoneyama H, Numata M, Uemura K, Usami Y, Harusawa S. J. Org. Chem. 2017; 82: 5538
12b Yoneyama H, Uemura K, Usami Y, Harusawa S. Tetrahedron 2017; 73: 6109
12c Yoneyama H, Hisaka F, Fujisue D, Usami Y, Zhao Z, Harusawa S. Heterocycles 2018; 96: 106
12d Yoneyama H, Uemura K, Usami Y, Harusawa S. Tetrahedron 2018; 74: 2143
12e Yoneyama H, Harusawa S. Heterocycles 2018; 96: 2037

13 Progesterone (3) was purchased from TCI Co., Ltd

For recent reviews on tetrazoles, see:

14a Bhatt U. Five-Membered Heterocycles with Four Heteroatoms: Tetrazoles . In Modern Heterocyclic Chemistry, Vol. 3. Alvarez-Builla J, Vaquero JJ, Barluenga J. Wiley-VCH; Weinheim: 2011: 1401-1430
14b Ostrovski VA, Popova EA, Trifonov RE. Developments in Tetrazole Chemistry (2009^_16) . In Advances in Heterocyclic Chemistry, Vol. 123. Scriven E, Ramsden CA. Academic Press; New York: 2017: 1-62

15 Harusawa S, Nakamura S, Yagi S, Kurihara T, Hamada Y, Shioiri T. Synth. Commun. 1984; 14: 1365
16 Wittenberger SJ, Donner BG. J. Org. Chem. 1993; 58: 4139
17 Yoneyama H, Usami Y, Komeda S, Harusawa S. Synthesis 2013; 45: 1051

Supplementary Material

Supporting Information