Total Synthesis and Anti-inflammatory Activity of Stemoamide-Type Alkaloids Including Totally Substituted Butenolides and Pyrroles

Yasuki Soda; Yasukazu Sugiyama; Shunsei Sato; Kana Shibuya; Junya Saegusa; Tomoe Matagawa; Sayaka Kawano; Makoto Yoritate; Keisuke Fukaya; Daisuke Urabe; Takeshi Oishi; Kento Mori; Siro Simizu; Noritaka Chida; Takaaki Sato

doi:10.1055/a-1941-8680

Synthesis, Table of Contents

Synthesis 2023; 55(04): 617-636
DOI: 10.1055/a-1941-8680

paper

Total Synthesis and Anti-inflammatory Activity of Stemoamide-Type Alkaloids Including Totally Substituted Butenolides and Pyrroles

Authors

Yasuki Soda

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Yasukazu Sugiyama

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Shunsei Sato

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Kana Shibuya

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Junya Saegusa

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Tomoe Matagawa

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Sayaka Kawano

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Makoto Yoritate

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Keisuke Fukaya

^bBiotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
Daisuke Urabe

^bBiotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
Takeshi Oishi

^cSchool of Medicine, Keio University, 4-1-1, Hiyoshi, Kohoku-ku, Yokohama 223-8521, Japan
Kento Mori

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Siro Simizu

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Noritaka Chida

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Takaaki Sato

^aDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan

Abstract

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Abstract

Totally substituted butenolide including two tetrasubstituted olefins is a distinct structural motif seen in Stemona alkaloids, but efficient methods for its synthesis are not well developed. As an ongoing program aimed at the collective total synthesis of the stemoamide group, we report a stereodivergent method to give either (E)- or (Z)-totally substituted butenolide from the same intermediate. While AgOTf-mediated elimination via an E1-type mechanism results in the formation of the kinetic (Z)-tetrasubstituted olefin, subsequent TfOH-mediated isomerization gives the thermodynamic (E)-tetrasubstituted olefin. The pyrrole ring is another important structure found in Stemona alkaloids. The direct oxidation of pyrrolidine rings with MnO₂ and careful purification gives the pyrrole groups without isomerization of the stereocenter in the lactone group. These two methods enabled us to synthesize a series of stemoamide-type alkaloids including tricyclic, tetracyclic, and pentacyclic frameworks. The anti-inflammatory activities by inhibition of iNOS expression in macrophage cell line RAW264.7 indicate that the most potent anti-inflammatory compounds without cytotoxicity are protostemonines, which consist of pentacyclic frameworks including the totally substituted butenolide.

Key words

amides - anti-inflammatory agents - butenolides - DFT calculations - iNOS - pyrroles - Stemona alkaloids - total synthesis

Full Text

References

References
1 New address: M. Yoritate, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

For reviews on Stemona alkaloids, see:

2a Pilli RA, de Oliveira MC. F. Nat. Prod. Rep. 2000; 17: 11
2b Greger H. Planta Med. 2006; 72: 99
2c Alibés R, Figueredo M. Eur. J. Org. Chem. 2009; 2421
2d Pilli RA, Rosso GB, de Oliveira MC. F. Nat. Prod. Rep. 2010; 27: 1908
2e Greger H. Phytochem. Rev. 2019; 18: 463
2f Iwata T, Shindo M. Heterocycles 2019; 98: 349
2g Liu Y, Shen Y, Teng L, Yang L, Cao K, Fu Q, Zhang J. J. Ethnopharmacol. 2021; 265: 113112

For isolation and structural determination of protostemonine (1) and isoprotostemonine (17), see:

3a Irie H, Harada H, Ohno K, Mizutani T, Uyeo S. J. Chem. Soc. D 1970; 268
3b Irie H, Ohno K, Osaki K, Taga T, Uyeo S. Chem. Pharm. Bull. 1973; 21: 451
3c Ye Y, Xu R.-S. Chin. Chem. Lett. 1992; 3: 511
3d Ye Y, Qin G.-W, Xu R.-S. Phytochemistry 1994; 37: 1205
3e Kaltenegger E, Brem B, Mereiter K, Kalchhauser H, Kählig H, Hofer O, Vajrodaya S, Greger H. Phytochemistry 2003; 63: 803

For biological activity of protostemonine (1), see:

4a Yang X.-Z, Zhu J.-Y, Tang C.-P, Ke C.-Q, Lin G, Cheng T.-Y, Rudd JA, Ye Y. Planta Med. 2009; 75: 174
4b Cheng Z, Yue L, Zhao W, Yang X, Shu G. Int. Immunopharmacol. 2015; 29: 798
4c Huang S.-Z, Kong F.-D, Ma Q.-Y, Guo Z.-K, Zhou L.-M, Wang Q, Dai H.-F, Zhao Y.-X. J. Nat. Prod. 2016; 79: 2599
4d Wu Y.-X, He H.-Q, Nie Y.-J, Ding Y.-H, Sun L, Qian F. Acta Pharmacol. Sin. 2018; 39: 85
4e Song Y, Wu Y, Li X, Shen Y, Ding Y, Zhu H, Liu F, Yu K, Sun L, Qian F. Biochem. Pharmacol. 2018; 155: 198
4f Wu Y, Nie Y, Huang J, Qiu Y, Wan B, Liu G, Chen J, Chen D, Pang Q. Int. Immunopharmacol. 2019; 77: 105964

5 Greger proposes another classification based on biosynthetic considerations; see refs. 2b and 2e.

For synthesis of the totally substituted butenolides and application to total synthesis of natural products, see:

6a Kende AS, Smalley TL. Jr, Huang H. J. Am. Chem. Soc. 1999; 121: 7431
6b Velázquez F, Olivo HF. Org. Lett. 2002; 4: 3175
6c Brüggemann M, McDonald AI, Overman LE, Rosen MD, Schwink L, Scott JP. J. Am. Chem. Soc. 2003; 125: 15284
6d Huang P.-Q, Huang S.-Y, Gao L.-H, Mao Z.-Y, Chang Z, Wang A.-E. Chem. Commun. 2015; 51: 4576
6e Huang X.-Z, Gao L.-H, Huang P.-Q. Nat. Commun. 2020; 11: 5314
6f Huang Y.-Q, Huang X.-Z, Huang P.-Q. J. Org. Chem. 2021; 86: 2359

7 For isolation of stemofoline (5) and isostemofoline (6), see: Irie H, Masaki N, Ohno K, Osaki K, Taga T, Uyeo S. J. Chem. Soc. D 1970; 1066
8 For total synthesis of stemofoline (5) and isostemofoline (6), see ref. 6.
9 For isolation of stemocurtisine (7), see: Mungkornasawakul P, Pyne SG, Jatisatienr A, Supyen D, Lie W, Ung AT, Skelton BW, White AH. J. Nat. Prod. 2003; 66: 980

For oxidation of the pyrrolidines to the pyrroles, see:

10a ref. 3a.
10b ref 3d.
10c Noro T, Fukushima S, Ueno A, Miyase T, Iitaka Y, Saiki Y. Chem. Pharm. Bull. 1979; 27: 1495
10d Bonnaud B, Bigg DC. H. Synthesis 1994; 465
10e Wipf P, Spencer SR. J. Am. Chem. Soc. 2005; 127: 225

For isolation of tuberostemonine (8), see:

11a Suzuki K. J. Pharm. Soc. Jpn. 1934; 54: 573
11b Schild H. Ber. Dtsch. Chem. Ges. B 1936; 69: 74
11c Kondo H, Suzuki K, Satomi M. J. Pharm. Soc. Jpn. 1939; 59: 443
11d Edwards OE, Feniak G. Can. J. Chem. 1962; 40: 2416
11e Götz M, Bögri T, Gray AH, Strunz GM. Tetrahedron 1968; 24: 2631

For isolation of bisdehydrotuberostemonine (9), see:

12a Ye Y, Qin G.-W, Xu R.-S. Phytochemistry 1994; 37: 1201
12b Lin W, Fu H. J. Chin. Pharm. Sci. 1999; 8: 1

For total synthesis of tuberostemonine (8) and bisdehydrotuberostemonine (9), see:

13a ref. 10e.
13b Deng Y, Liang X, Wei K, Yang Y.-R. J. Am. Chem. Soc. 2021; 143: 20622

For isolation of croomine (10) and didehydrocroomine (11), see:

14a ref. 10c.
14b Hu Z.-X, Tang H.-Y, Guo J, Aisa HA, Zhang Y, Hao X.-J. Tetrahedron 2019; 75: 1711

For total synthesis of croomine (10), see:

15a Williams DR, Brown DL, Benbow JW. J. Am. Chem. Soc. 1989; 111: 1923
15b Martin SF, Barr KJ. J. Am. Chem. Soc. 1996; 118: 3299
15c Martin SF, Barr KJ, Smith DW, Bur SK. J. Am. Chem. Soc. 1999; 121: 6990

16 For isolation of stemoamide (12), see: Lin W.-H, Ye Y, Xu R.-S. J. Nat. Prod. 1992; 55: 571

For total synthesis of stemoamide (12), see:

17a Williams DR, Reddy JP, Amato GS. Tetrahedron Lett. 1994; 35: 6417
17b Kohno Y, Narasaka K. Bull. Chem. Soc. Jpn. 1996; 69: 2063
17c Kinoshita A, Mori M. J. Org. Chem. 1996; 61: 8356
17d Jacobi PA, Lee K. J. Am. Chem. Soc. 1997; 119: 3409
17e Kinoshita A, Mori M. Heterocycles 1997; 46: 287
17f Jacobi PA, Lee K. J. Am. Chem. Soc. 2000; 122: 4295
17g Sibi MP, Subramanian T. Synlett 2004; 1211
17h Olivo HF, Tovar-Miranda R, Barragán E. J. Org. Chem. 2006; 71: 3287
17i Torssell S, Wanngren E, Somfai P. J. Org. Chem. 2007; 72: 4246
17j Bates RW, Sridhar S. Synlett 2009; 1979
17k Honda T, Matsukawa T, Takahashi K. Org. Biomol. Chem. 2011; 9: 673
17l Wang Y, Zhu L, Zhang Y, Hong R. Angew. Chem. Int. Ed. 2011; 50: 2787
17m Mi X, Wang Y, Zhu L, Wang R, Hong R. Synthesis 2012; 44: 3432
17n Li Z, Zhang L, Qiu FG. Asian J. Org. Chem. 2014; 3: 52
17o Nakayama Y, Maeda Y, Hama N, Sato T, Chida N. Synthesis 2016; 48: 1647
17p Yoritate M, Takahashi Y, Tajima H, Ogihara C, Yokoyama T, Soda Y, Oishi T, Sato T, Chida N. J. Am. Chem. Soc. 2017; 139: 18386
17q Yin X, Ma K, Dong Y, Dai M. Org. Lett. 2020; 22: 5001
17r Siitonen JH, Csókás D, Pápai I, Pihko PM. Synlett 2020; 31: 1581
17s Soda Y, Sugiyama Y, Yoritate M, Tajima H, Shibuya K, Ogihara C, Oishi T, Sato T, Chida N. Org. Lett. 2020; 22: 7502
17t Guo Z, Bao R, Li Y, Li Y, Zhang J, Tang Y. Angew. Chem. Int. Ed. 2021; 60: 14545
17u Cao F, Gao W, Wang X, Zhang Z, Yin G, Wang Y, Li Z, Shi T, Hou Y, Chen J, Wang Z. Org. Lett. 2021; 23: 6222
17v Sugiyama Y, Soda Y, Yoritate M, Tajima H, Takahashi Y, Shibuya K, Ogihara C, Yokoyama T, Oishi T, Sato T, Chida N. Bull. Chem. Soc. Jpn. 2022; 95: 278

18 For our approach using chemoselective assembly of five-membered building blocks, see refs. 17p, 17s, and 17v.
19 Part of this work was published as a preliminary communication; see ref. 17s.
20 Stemoamide (12) was prepared in 7 steps from commercially available ethyl 4-bromobutanoate; see ref. 17v.
21 For isolation of protostemonamide (14), see ref. 4a.

For selected reviews on nucleophilic addition to amides, see:

22a Seebach D. Angew. Chem. Int. Ed. 2011; 50: 96
22b Murai T, Mutoh Y. Chem. Lett. 2012; 41: 2
22c Sato T, Chida N. Org. Biomol. Chem. 2014; 12: 3147
22d Pace V, Holzer W, Olofsson B. Adv. Synth. Catal. 2014; 356: 3697
22e Volkov A, Tinnis F, Slagbrand T, Trillo P, Adolfsson H. Chem. Soc. Rev. 2016; 45: 6685
22f Więcław MM, Stecko S. Eur. J. Org. Chem. 2018; 6601
22g Sato T, Yoritate M, Tajima H, Chida N. Org. Biomol. Chem. 2018; 16: 3864
22h Kaiser D, Bauer A, Lemmerer M, Maulide N. Chem. Soc. Rev. 2018; 47: 7899
22i Huang P.-Q. Acta Chim. Sin. 2018; 76: 357
22j Matheau-Raven D, Gabriel P, Leitch JA, Almehmadi YA, Yamazaki K, Dixon DJ. ACS Catal. 2020; 10: 8880
22k Ong DY, Chen J.-h, Chiba S. Bull. Chem. Soc. Jpn. 2020; 93: 1339
22l Czerwiński PJ, Furman B. Front. Chem. 2021; 9: 655849

For recent selected examples of nucleophilic addition to amides, see:

23a Xia Q, Ganem B. Org. Lett. 2001; 3: 485
23b Murai T, Mutoh Y, Ohta Y, Murakami M. J. Am. Chem. Soc. 2004; 126: 5968
23c Murai T, Asai F. J. Am. Chem. Soc. 2007; 129: 780
23d Xiao K.-J, Luo J.-M, Ye K.-Y, Wang Y, Huang P.-Q. Angew. Chem. Int. Ed. 2010; 49: 3037
23e Shirokane K, Kurosaki Y, Sato T, Chida N. Angew. Chem. Int. Ed. 2010; 49: 6369
23f Vincent G, Guillot R, Kouklovsky C. Angew. Chem. Int. Ed. 2011; 50: 1350
23g Bélanger G, O’Brien G, Larouche-Gauthier R. Org. Lett. 2011; 13: 4268
23h Bechara WS, Pelletier G, Charette AB. Nat. Chem. 2012; 4: 228
23i Medley JW, Movassaghi M. Angew. Chem. Int. Ed. 2012; 51: 4572
23j Xiao K.-J, Wang A.-E, Huang P.-Q. Angew. Chem. Int. Ed. 2012; 51: 8314
23k Jakubec P, Hawkins A, Felzmann W, Dixon DJ. J. Am. Chem. Soc. 2012; 134: 17482
23l Bonazzi S, Cheng B, Wzorek JS, Evans DA. J. Am. Chem. Soc. 2013; 135: 9338
23m Jäkel M, Qu J, Schnitzer T, Helmchen G. Chem. Eur. J. 2013; 19: 16746
23n Shirokane K, Wada T, Yoritate M, Minamikawa R, Takayama N, Sato T, Chida N. Angew. Chem. Int. Ed. 2014; 53: 512
23o Szcześniak P, Stecko S, Staszewska-Krajewska O, Furman B. Tetrahedron 2014; 70: 1880
23p Gregory AW, Chambers A, Hawkins A, Jakubec P, Dixon DJ. Chem. Eur. J. 2015; 21: 111
23q Nakajima M, Sato T, Chida N. Org. Lett. 2015; 17: 1696
23r Katahara S, Kobayashi S, Fujita K, Matsumoto T, Sato T, Chida N. J. Am. Chem. Soc. 2016; 138: 5246
23s Huang P.-Q, Ou W, Han F. Chem. Commun. 2016; 52: 11967
23t Huang P.-Q, Lang Q.-W, Hu X.-N. J. Org. Chem. 2016; 81: 10227
23u Tan PW, Seayad J, Dixon DJ. Angew. Chem. Int. Ed. 2016; 55: 13436
23v Sato M, Azuma H, Daigaku A, Sato S, Takasu K, Okano K, Tokuyama H. Angew. Chem. Int. Ed. 2017; 56: 1087
23w Fuentes de Arriba ÁL, Lenci E, Sonawane M, Formery O, Dixon DJ. Angew. Chem. Int. Ed. 2017; 56: 3655
23x ref. 17p.
23y Xie L.-G, Dixon DJ. Chem. Sci. 2017; 8: 7492
23z Xie L.-G, Dixon DJ. Nat. Commun. 2018; 9: 2841
23aa Ou W, Han F, Hu X.-N, Chen H, Huang P.-Q. Angew. Chem. Int. Ed. 2018; 57: 11354
23ab Takahashi Y, Yoshii R, Sato T, Chida N. Org. Lett. 2018; 20: 5705
23ac Trillo P, Slagbrand T, Adolfsson H. Angew. Chem. Int. Ed. 2018; 57: 12347
23ad Hiraoka S, Matsumoto T, Matsuzaka K, Sato T, Chida N. Angew. Chem. Int. Ed. 2019; 58: 4381
23ae Takahashi Y, Sato T, Chida N. Chem. Lett. 2019; 48: 1138
23af Trillo P, Adolfsson H. ACS Catal. 2019; 9: 7588
23ag Ong DY, Fan D, Dixon DJ, Chiba S. Angew. Chem. Int. Ed. 2020; 59: 11903
23ah ref. 17s.
23ai Rogova T, Gabriel P, Zavitsanou S, Leitch JA, Duarte F, Dixon DJ. ACS Catal. 2020; 10: 11438
23aj Katahara S, Sugiyama Y, Yamane M, Komiya Y, Sato T, Chida N. Org. Lett. 2021; 23: 3058
23ak Yamazaki K, Gabriel P, Carmine GD, Pedroni J, Farizyan M, Hamlin TA, Dixon DJ. ACS Catal. 2021; 11: 7489
23al Chen D.-H, Sun W.-T, Zhu C.-J, Lu G.-S, Wu D.-P, Wang A.-E, Huang P.-Q. Angew. Chem. Int. Ed. 2021; 60: 8827
23am Gabriel P, Almehmadi YA, Wong ZR, Dixon DJ. J. Am. Chem. Soc. 2021; 143: 10828
23an Matheau-Raven D, Dixon DJ. Angew. Chem. Int. Ed. 2021; 60: 19725

24 For isolation of bisdehydroprotostemonine (18), see refs. 3c and 3d.

For selected total synthesis of other tetracyclic and pentacyclic stemoamide-type alkaloids, see:

25a Williams DR, Fromhold MG, Earley JD. Org. Lett. 2001; 3: 2721
25b Liu X.-K, Ye J.-L, Ruan Y.-P, Li Y.-X, Huang P.-Q. J. Org. Chem. 2013; 78: 35
25c Ma K, Yin X, Dai M. Angew. Chem. Int. Ed. 2018; 57: 15209
25d Hou Y, Shi T, Yang Y, Fan X, Chen J, Cao F, Wang Z. Org. Lett. 2019; 21: 2952

For preparation of model lactone 31, see:

26a Nemoto H, Nagai M, Fukumoto K. J. Org. Chem. 1985; 50: 2764
26b Fujita M, Kitagawa O, Izawa H, Dobashi A, Fukaya H, Taguchi T. Tetrahedron Lett. 1999; 40: 1949

27 For an example of bromination of butenolides, see: Sum F.-W, Weiler L. J. Org. Chem. 1979; 44: 1012
28 For determination of the stereochemistry of the tetrasubstituted olefins in 37, see the Supporting Information.
29 The AgOTf-mediated elimination of bromides 38 in the absence of 3 Å molecular sieves indicated partial formation of hemiacetals such as 51 shown in Figure 3. Hemiacetal 51 was separately obtained by hydration of 38d in THF/H₂O (1:1) at 70 °C.
30 Although oxidative cleavage of model compounds 37, protostemonine (1), and isoprotostemonine (17) was not observed, all compounds including the totally substituted butenolides were stored in a glovebox.
31 The Gibbs free energy of (Z)-37 is 0.4 kcal/mol lower than that of (E)-37, which is consistent with the experimental trend for the isomerization; see the Supporting Information. The Huang group proposed the preferential formation of the (Z)-isomer without the methyl group might be understood due to repulsion by electron pair–electron pair interaction of the (E)-isomer; see ref. 6f.

For isolation of stemonine (41), see:

32a Suzuki K. J. Pharm. Soc. Jpn. 1929; 49: 457
32b Suzuki K. J. Pharm. Soc. Jpn. 1931; 51: 419
32c Koyama H, Oda K. J. Chem. Soc. B 1970; 1330

For total synthesis of stemonine (41), see:

33a Williams DR, Shamim K, Reddy JP, Amato GS, Shaw SM. Org. Lett. 2003; 5: 3361
33b refs. 17p, 17t, and 17v.

34 For epimerization of the pyrrole-type alkaloids, see refs. 25c and 13b.
35 For isolation of didehydrostemonine (42), see: Changying Z, Jun L, Haimin L, Hongzheng F, Wenhan L. J. Chin. Pharm. Sci. 2000; 9: 113

36a Motoyama Y, Aoki M, Takaoka N, Aoto R, Nagashima H. Chem. Commun. 2009; 1574

Curtis reported the synthesis of siloxane oligomer using (Me₂HSi)₂O and a catalytic amount of the Vaska complex [IrCl(CO)(PPh₃)₂]; see:

36b Greene J, Curtis MD. J. Am. Chem. Soc. 1977; 99: 5176

37a Rosso GB, Pilli RA. Tetrahedron Lett. 2006; 47: 185
37b Funakoshi Y, Miura T, Murakami M. Org. Lett. 2016; 18: 6284

For selected reviews on iNOS, see:

38a Kleinert H, Pautz A, Linker K, Schwarz PM. Eur. J. Pharmacol. 2004; 500: 255
38b Pautz A, Art J, Hahn S, Nowag S, Voss C, Kleinert H. Nitric Oxide 2010; 23: 75

39 For examples of LPS-induced iNOS expression, see: Jin Y, Liu Y, Nelin LD. J. Biol. Chem. 2015; 290: 2099
40 For iNOS expression, bisdehydroprotostemonine (18) and isobisdehydroprotostemonine (19) were examined as a diastereomeric mixture [18 (β-H)/epi-18 (α-H) = 2.5:1, 19 (β-H)/epi-19 (α-H) = 2.5:1] because they are prone to undergo quick epimerization at C18; see the experimental.
41 MacroModel . Schrödinger, LLC; New York (NY, USA): 2021
42 Gaussian 16, Revision C.01 . Gaussian, Inc; Wallingford (CT, USA): 2019

43a Simizu S, Imoto M, Umezawa K. Biosci., Biotechnol., Biochem. 1994; 58: 1549
43b Komai K, Niwa Y, Sasazawa Y, Simizu S. FEBS Lett. 2015; 589: 738
43c Morishita S, Suzuki T, Niwa Y, Dohmae N, Simizu S. Oncol. Lett. 2017; 14: 2537

44a Tamura Y, Simizu S, Muroi M, Takagi S, Kawatani M, Watanabe N, Osada H. Oncogene 2009; 28: 107
44b Miura K, Kawano S, Suto T, Sato T, Chida N, Simizu S. Bioorg. Med. Chem. 2021; 34: 116041

45 Miyazaki S, Sasazawa Y, Mogi T, Suzuki T, Yoshida K, Dohmae N, Takao K, Simizu S. FEBS Lett. 2016; 590: 1163
46 Katsuyama S, Sugino K, Sasazawa Y, Nakano Y, Aono H, Morishita K, Kawatani M, Umezawa K, Osada H, Simizu S. FEBS Lett. 2016; 590: 1152

Supplementary Material

Supporting Information (PDF) (opens in new window)