Highly Stereoselective Formal Synthesis of Rosuvastatin and Pitavastatin Through Julia–Kocienski Olefination Using the Lactonized Statin Side-Chain Precursor

Jan Fabris; Zdenko Časar; Ivana Gazić Smilović; Martin Črnugelj

doi:10.1055/s-0033-1338648

Synthesis, Table of Contents

Synthesis 2014; 46(17): 2333-2346
DOI: 10.1055/s-0033-1338648

paper

Highly Stereoselective Formal Synthesis of Rosuvastatin and Pitavastatin Through Julia–Kocienski Olefination Using the Lactonized Statin Side-Chain Precursor

Jan Fabris

^aCadonic Consultancy Services, LL.C., Cesta na postajo 74, 1351 Brezovica pri Ljubljani, Slovenia

^bLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia

,

Zdenko Časar*

^bLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia

^cFaculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia

^dSandoz GmbH, Global Portfolio Management API, Biochemiestrasse 10, 6250 Kundl, Austria Fax: +43(5338)200418 Email: zdenko.casar@sandoz.com

,

Ivana Gazić Smilović

^bLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia

,

Martin Črnugelj

^bLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Kolodvorska 27, 1234 Mengeš, Slovenia

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Abstract

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Abstract

An expedient and simple synthetic approach to pitavastatin and rosuvastatin final intermediates is described. The presented approach consists of completely stereoselective Julia–Kocienski olefination step (E/Z up to 300:1) between lactonized statin side-chain precursor and sulfone derivative of the corresponding pyrimidine and quinoline heterocyclic cores. The desired O-TBS protected statin lactones were isolated in 66–71% yield and high >97% purity (HPLC).

Key words

stereoselective synthesis - olefination - heterocycles - sulfones - lactones - aldehydes - drugs

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References

References

1a Istvan ES, Deisenhofer J. Science 2001; 292: 1160
1b Singh N, Tamariz J, Chamorro G, Medina-Franco JL. Mini-Rev. Med. Chem. 2009; 9: 1272
1c Haines BE, Wiest O, Stauffacher CV. Acc. Chem. Res. 2013; 46: 2416

2a Kidd J. Nat. Rev. Drug Discovery 2006; 5: 813
2b Endo A. Nat. Med. 2008; 14: 1050

3 Tobert JA. Nat. Rev. Drug Discovery 2003; 2: 517

4a Davidson MH, Robinson JG. Expert Opin. Pharmacother. 2006; 7: 1701
4b Reiner Ž. Nat. Rev. Cardiol. 2013; 10: 453

5a Endo A, Kuroda M, Tsujita Y. J. Antibiot. 1976; 29: 1346
5b Endo A, Tsujita Y, Kuroda M, Tanzawa K. Eur. J. Biochem. 1977; 77: 31
5c Endo A. J. Lipid Res. 1992; 33: 1569
5d Endo A, Hasumi K. Nat. Prod. Rep. 1993; 10: 541

Also known as mevinolin, with a brand name of Mevacor^® (Merck & Co). For selected literature, see:

6a Endo A. J. Antibiot. 1979; 32: 852
6b Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Albers-Schonberg G, Hensens O, Hirshfield J, Hoogsteen K, Liesch J, Springer J. Proc. Natl. Acad. Sci. U.S.A. 1980; 77: 3957

7 Also known as velostatin, with a brand name of Zocor^® (Merck & Co). For selected literature, see: Hoffman WF, Alberts AW, Anderson PS, Chen JS, Smith RL, Willard AK. J. Med. Chem. 1986; 29: 849
8 FDA approved in 1996, also known as eptastatin with a brand name of Pravachol^® (Bristol–Myers Squibb). For selected literature, see: Tsujita Y, Kuroda M, Shimada Y, Tanzawa K, Arai M, Kaneko I, Tanaka M, Masuda H, Tarumi C, Watanabe Y. Biochim. Biophys. Acta 1986; 877: 50

9a Časar Z. Curr. Org. Chem. 2010; 14: 816
9b Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432

10 McPherson PA. C. Mini-Rev. Med. Chem. 2012; 12: 1250
11 FDA approved in 1993, with a brand name of Lescol^® (Novartis Pharma AG). For selected literature, see: Fuenfschilling PC, Pascale H, Mutz J.-P. Org. Process Res. Dev. 2007; 11: 13 ; and references cited therein
12 FDA approved in 1996, with a brand name of Lipitor^® [Pfizer (Parke–Davis)]. For selected literature, see: Roth BD, Blankley CJ, Chucholowski AW, Ferguson E, Hoefle ML, Ortwine DF, Newton RS, Sekerke CS, Sliskovic DR, Stratton CD, Wilson M. J. Med. Chem. 1991; 34: 357
13 FDA approved in 2003, with a brand name of Crestor^® (AstraZeneca). For selected literature, see: Watanabe M, Koike H, Ishiba T, Okada T, Sea S, Hirai K. Bioorg. Med. Chem. 1997; 5: 437
14 The last super-statin group member pitavstatin with a brand name of Livalo^® (Kowa Company, Ltd.) was launched in Japan in 2003 and approved by FDA in 2009 and entered the US market in 2010. For selected literature, see: Watson KE. Rev. Cardiovas. Med. 2010; 11: 26
15 Soran H, Durrington P. Expert Opin. Pharmacother. 2008; 9: 2145

16a Kajinami K, Mabuchi H, Saito Y. Expert Opin. Invest. Drugs 2000; 9: 2653
16b Iglestas P, Díez JJ. Expert Opin. Invest. Drugs 2003; 12: 1777
16c Scharnagl H, März W. Curr. Top. Med. Chem. 2005; 5: 233
16d Mukhtar RY. A, Reid J, Reckless JP. D. Int. J. Clin. Pract. 2005; 59: 239
16e Hayashi T, Yokote K, Saito Y, Iguchi A. Expert Opin. Pharmacother. 2007; 8: 2315
16f Wensel TM, Waldrop BA, Wensel B. Ann. Pharmacother. 2010; 44: 507
16g Ahmad H, Cheng-Lai A. Cardiol. Rev. 2010; 18: 264
16h Gotto AM. Jr, Moon J. Expert Rev. Cardiovasc. Ther. 2010; 8: 1079
16i Ohbayashi H. Drugs Today 2010; 46: 765
16j Baker WL, Datta R. Adv. Ther. 2011; 28: 13
16k Kawai Y, Sato-Ishida R, Motoyama A, Kouji K. Drug Des. Devel. Ther. 2011; 5: 283
16l Yee LL, Wright EA. Clin. Ther. 2011; 33: 1023
16m Corsini A, Ceska R. Curr. Med. Res. Opin. 2011; 27: 1551

17a Balanov A, Shenkar N, Niddam-Hildesheim V. US Patent Appl. US 2007167625 A1, 2007 ; Chem. Abstr. 2007, 147, 166109.
17b Radl S, Stach J, Klvana R, Jirman J. PCT Patent Appl. WO 2007000121 A1, 2007 ; Chem. Abstr. 2007, 146, 121983.
17c Patel DJ, Kumar R, Dwivedi SP. D. PCT Patent Appl. WO 2007099561 A1, 2007 ; Chem. Abstr. 2007, 147, 322770.
17d Žličar M. PCT Patent Appl. WO 2007017117, 2007 ; Chem. Abstr. 2007, 146, 251655.
17e Andrushko N, Andrushko V, König G, Spannenberg A, Börner A. Eur. J. Org. Chem. 2008; 847

For reviews on synthesis of pitavastatin, see:

18a Miyachi N, Suzuki M, Ohara Y, Hiyama T. J. Synth. Org. Chem. Jpn. 1995; 53: 186
18b Sorbera LA, Leeson PA, Castaner J. Drugs Fut. 1998; 23: 847

For the non-Wittig and non-HWE synthesis of pitavastatin, see:

19a Takano S, Kamikubo T, Sugihara T, Suzuki M, Ogasawara K. Tetrahedron: Asymmetry 1993; 4: 201
19b Takahashi K, Minami T, Ohara Y, Hiyama T. Tetrahedron Lett. 1993; 34: 8263
19c Miyachi N, Yanagawa Y, Iwasaki H, Ohara Y, Hiyama T. Tetrahedron Lett. 1993; 34: 8267
19d Takahashi K, Minami T, Ohara Y, Hiyama T. Bull. Chem. Soc. Jpn. 1995; 68: 2649
19e Hiyama T, Minami T, Takahashi K, Miyachi N, Ohara Y. PCT Patent Int. Appl. WO 9406746, 1994 ; Chem. Abstr. 1994, 122, 105264.
19f Suzuki M, Yanagawa Y, Iwasaki H, Kanda H, Yanagihara K, Matsumoto H, Ohara Y, Yazaki Y, Sakoda R. Bioorg. Med. Chem. Lett. 1999; 9: 2977
19g Suzuki M, Iwasaki H, Fujikawa Y, Kitahara M, Sakashita M, Sakoda R. Bioorg. Med. Chem. 2001; 9: 2727
19h Chen G.-P, Kapa PK, Loeser EM, Beutler U, Zaugg W, Girgis MJ. PCT Patent Appl. WO 2003064382, 2003 ; Chem. Abstr. 2003, 139, 164712.
19i Manne SR, Bairy KR, Chepyala KR, Muppa KK, Srinivasan RT, Sajja E, Maramreddy SR. Orient. J. Chem. 2007; 23: 559

20a Minami T, Hiyama T. Tetrahedron Lett. 1992; 33: 7525
20b Minami T, Takahashi K, Hiyama T. Tetrahedron Lett. 1993; 34: 513
20c Hiyama T, Minami T, Takahashi K. Bull. Chem. Soc. Jpn. 1995; 68: 364
20d Hiyama T, Minami T, Yanagawa Y, Ohara Y. PCT Patent Int. Appl. WO 9511898, 1995 ; Chem. Abstr. 1995, 123, 313782.

21 Acemoglu M, Brodbeck A, Garcia A, Grimler D, Hassel M, Riss B, Schreiber R. Helv. Chim. Acta 2007; 90: 1069

For reviews on Julia–Kocienski olefination, see:

22a Blakemore PR. J. Chem. Soc., Perkin Trans. 1 2002; 2563
22b Plesniak K, Zarecki A, Wicha J. Top. Curr. Chem. 2007; 275: 163
22c Aïssa C. Eur. J. Org. Chem. 2009; 1831
22d Yanai H, Taguchi T. Eur. J. Org. Chem. 2011; 5939

For representative papers and mechanistic discussions on Julia–Kocienski olefination, see:

23a Julia M, Paris J.-M. Tetrahedron Lett. 1973; 4833
23b Blakemore PR, Cole WJ, Kocienski PJ, Morley A. Synlett 1998; 26
23c Charette AB, Berthelette C, St-Martin D. Tetrahedron Lett. 2001; 42: 5149
23d Mirk D, Grassot J.-M, Zhu J. Synlett 2006; 1255
23e Lebrun M.-E, Le Marquand P, Berthelette C. J. Org. Chem. 2006; 71: 2009
23f Pospišil J. Tetrahedron Lett. 2011; 52: 2348
23g Robiette R, Pospíšil J. Eur. J. Org. Chem. 2013; 836
23h Habib S, Larnaud F, Pfund E, Lequeux T, Fenet B, Goekjian PG, Gueyrard D. Eur. J. Org. Chem. 2013; 1872
23i Hafner A, Fischer TS, Bräse S. Eur. J. Org. Chem. 2013; 7996

For patent literature related to the synthesis of statins via Julia–Kocienski olefination with aldehyde type dually protected open side-chain derivatives D, see:

24a Ju H, Joung S.-S, Yi H.-J, Khoo J.-H, Lim J.-C, Kim J.-G. PCT Patent Appl. WO 2012002741, 2012 ; Chem. Abstr. 2012, 156, 122219.
24b Pandya VP, Richhariya S, Divya P, Meeran HN. P. N, Tewari N. PCT Patent Appl. WO 2011132172, 2011 ; Chem. Abstr. 2011, 155, 589162.
24c Reddy MS, Rajan ST, Reddy MS. PCT Patent Appl. WO 2011083495, 2011 ; Chem. Abstr. 2011, 155, 182074.
24d Reddy MS, Rajan ST, Reddy MS. PCT Patent Appl. WO 2011086584, 2011 ; Chem. Abstr. 2011, 155, 182078.
24e Kim HS, Kim WJ, Kim HC, Sim JY, Cho SM, Byun EY, Jeon JY, Lee YJ, Suh KH, Lee GS. PCT Patent Appl. WO 2010077062, 2010 ; Chem. Abstr. 2010, 153, 174956.
24f Kim HS, Kim H, Sim JY, Cho SM, Kim WJ, Suh KH, Lee GS. PCT Patent Appl. WO 2010098583, 2010 ; Chem. Abstr. 2010, 153, 334077.
24g Anegondi SP, Rajmahendra S, Joseph J, Srinivas PV. PCT Patent Appl. WO 2010023678, 2010 ; Chem. Abstr. 2010, 152, 287413.
24h Reddy MS, Rajan ST, Reddy MS. PCT Patent Appl. WO 2008044243, 2008 ; Chem. Abstr. 2008, 148, 471771.
24i Reddy MS, Rajan ST, Reddy MS. PCT Patent Appl. WO 2007125547, 2007 ; Chem. Abstr. 2007, 147, 522015.
24j Brodfuehrer PR, Sattelberg TR. Sr, Kant J, Qian X. PCT Patent Appl. WO 2002098854, 2002 ; Chem. Abstr. 2002, 138, 24717.

25 Hobson LA, Akiti O, Deshmukh SS, Harper S, Katipally K, Chiajen J, Livingston RC, Lo E, Miller MM, Ramakrishnan S, Shen L, Spink J, Tummala S, Wei C, Yamamoto K, Young J, Parsons RL. Org. Process Res. Dev. 2010; 14: 44

26a Časar Z. PCT Patent Int. Appl. WO 2007039287, 2007 ; Chem. Abstr. 2007, 146, 421841.
26b Časar Z, Steinbücher M, Košmrlj J. J. Org. Chem. 2010; 75: 6681
26c McLaughlin M, Garci Rubio S, Wilson I, Delaney P, Zhao W, Zlota A, Laird T. Org. Process Res. Dev. 2010; 14: 1276
26d Šterk D, Časar Z, Jukič M, Košmrlj J. Tetrahedron 2012; 68: 2155
26e Šterk D, Jukič M, Časar Z. Org. Process Res. Dev. 2013; 17: 145
26f Fabris J, Makuc D, Časar Z, Plavec J. Tetrahedron 2013; 69: 6262

27a Fabris J, GazićSmilović I, Časar Z. Synthesis 2012; 44: 1700
27b Makuc D, Fabris J, Časar Z, Plavec J. Molecules 2013; 18: 13283

28a Časar Z. Synlett 2008; 2036
28b Časar Z, Košmrlj J. Synlett 2009; 1144
28c Cluzeau J, Časar Z, Mrak P, Ošlaj M, Kopitar G. PCT Patent Int. Appl. WO 2009092702, 2009 ; Chem. Abstr. 2009, 151, 218948
28d Časar Z, Tramšek M, Goršek A. Acta Chim. Slov. 2010; 57: 66
28e Troiani V, Cluzeau J, Časar Z. Org. Process Res. Dev. 2011; 15: 622
28f Ošlaj M, Cluzeau J, Orkić D, Kopitar G, Mrak P, Časar Z. PLoS One 2013; 8: e62250
28g Turner K. Org. Process Res. Dev. 2013; 17: 893

29 El-Azab AS, Al-Omar MA, Abdel-Aziz AA, Abdel-Aziz NI, El-Sayed MA, Aleisa AM, Sayed-Ahmed MM, Abdel-Hamid SG. Eur. J. Med. Chem. 2010; 45: 4188
30 Zhu L, Ni C, Zhao Y, Hu J. Tetrahedron 2010; 66: 5089
31 Ringger DH, Chen P. Angew. Chem. Int. Ed. 2013; 52: 4686

32a Klemm LH, Mathur SB, Zell R, Merrill RE. J. Heterocycl. Chem. 1971; 8: 931
32b Sulfoxides have a band between 1040 and 1050 cm^–1, sulfones exhibit a symmetrical stretch between 1165 and 1170 cm^–1 and an asymmetrical stretch between 1300 and 1330 cm^–1, whereas N-oxides show a band between 1210 and 1265 cm^–1.

33 Sun M, Dai W, Liu DQ. J. Mass Spectrom. 2008; 43: 383

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