Asymmetric Total Synthesis of (2E)-Macrolactin 3

Aedula Vishnu V. Reddy; Utkal Mani Choudhury; Akella V. S. Sarma; Debendra K. Mohapatra

doi:10.1055/a-1957-3966

Synlett, Inhaltsverzeichnis

Synlett 2023; 34(01): 67-72
DOI: 10.1055/a-1957-3966

letter

Asymmetric Total Synthesis of (2E)-Macrolactin 3

Aedula Vishnu V. Reddy

^aDepartment of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India

^cAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India

,

Utkal Mani Choudhury

^aDepartment of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India

^cAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India

,

Akella V. S. Sarma

^bCentre for NMR and Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India

^cAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India

,

Debendra K. Mohapatra∗

^aDepartment of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India

^cAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Dedicated to Dr. Mukund K. Gurjar on the occasion of his 70^th birthday

Abstract

Asymmetric total synthesis of (2E)-macrolactin 3 has been accomplished in a highly convergent manner utilizing our earlier developed tandem isomerization followed by C–O and C–C bond-forming reaction, Sharpless asymmetric dihydroxylation, and a late-stage intramolecular Heck coupling reaction. Comparison of the NMR spectra of the coupled product and thorough analysis of the 2D NMR data of the final compound led to the conclusion that the Z-double bond at C2 was isomerized during the coupling reaction.

Key words

macrolactin - natural products - asymmetric synthesis - isomerization/C–O/C–C - Heck coupling

Volltext

Referenzen

References and Notes
1 Edmond MB, Ober JF, Weinbaum DL, Pfaller MA, Hwang T, Sanford MD, Wenzel RP. Clin. Infect. Dis. 1995; 20: 1126
2 Katz ML, Mueller LV, Polyakov M, Weinstock SF. Nat. Biotechnol. 2006; 24: 1529
3 Kong DX, Jiang YY, Zhang HY. Drug Discov. Today 2010; 15: 884
4 Molinski TF, Dalisay DS, Lievens SL, Saludes JP. Nat. Rev. Drug Discov. 2009; 8: 69
5 Bhatnagar I, Kim SK. Mar. Drugs 2010; 8: 2673

6a Liu Y. J. Mar. Sci.: Res. Dev. 2012; 2: e106
6b Newman DJ, Cragg GM. J. Nat. Prod. 2020; 83: 770

7 Gustafson K, Roman M, Fenical W. J. Am. Chem. Soc. 1989; 111: 7519
8 Mondol MA. M, Shin HJ, Islam MT. Mar. Drugs 2013; 11: 2846 ; and references therein
9 Mondol MA. M. Tareq F. S, Kin JH, Lee M, Lee H.-S, Lee Y.-J, Lee JS, Shin HJ. J. Nat. Prod. 2011; 74: 2582

10a Krishna PR, Rajesh N, Ramakrishna KV. S. Tetrahedron Lett. 2014; 55: 3381
10b Thodupunuri P, Hanumaiah M, Bommagani S, Sharma GV. M. J. Carbohydr. Chem. 2017; 36: 100
10c Reddy AM, Sabitha G. SynOpen 2017; 1: 166

11a Mallampudi NA, Srinivas B, Reddy JG, Mohapatra DK. Org. Lett. 2019; 21: 5952
11b Srinivas B, Reddy DS, Mallampudi NA, Mohapatra DK. Org. Lett. 2018; 20: 6910
11c Pradhan TR, Mohapatra DK. Org. Biomol. Chem. 2018; 16: 8810
11d Reddy GS, Padhi B, Bharath Y, Mohapatra DK. Org. Lett. 2017; 19: 6506
11e Mohapatra DK, Bhimireddy E, Krishnarao PS, Das PP, Yadav JS. Org. Lett. 2011; 13: 744

12 Mohapatra DK, Das PP, Pattanayak MR, Yadav JS. Chem. Eur. J. 2010; 16: 2072

13a Tokunaga M, Larrow JF, Kakiuchi F, Jacobsen EN. Science 1997; 227: 936
13b Schaue SE, Brandes BD, Larrow JF, Tokunaga M, Hansen KB, Gould AE, Furrow ME, Jacobsen EN. J. Am. Chem. Soc. 2002; 124: 1307
13c Nielson LP. C, Stevenson CP, Blackmond DG, Jacobsen EN. J. Am. Chem. Soc. 2004; 126: 1360

14 Yu W, Mei Y, Hua Z, Jin Z. Org. Lett. 2004; 6: 3217

15a Corey EJ, Gras JL, Ulrich P. Tetrahedron Lett. 1976; 17: 809
15b Bhatt MV, Kulkarni SU. Synthesis 1983; 249
15c Reddy DS, Gaddam J, Devunuri N, Mohapatra DK. Tetrahedron Lett. 2015; 56: 4299
15d Seetharamsingh B, Ganesh R, Reddy DS. J. Nat. Prod. 2017; 80: 560

16a Yu XM, Han H, Blagg BS. J. J. Org. Chem. 2005; 70: 5599
16b Lim W, Kim J, Rhee YH. J. Am. Chem. Soc. 2014; 136: 13618
16c Crimmins MT, Zuccarello JL, Pamela AC, Parrish JD. Org. Lett. 2006; 8: 159

17a Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
17b Noe MC, Letavic MA, Snow SL, McCombie SW. Org. React. 2005; 66: 109

18a Sinha SC, Sinha A, Yazbak A, Keinan E. J. Org. Chem. 1996; 61: 7640
18b Boyer FD, Hanna I, Nolan SP. J. Org. Chem. 2001; 66: 4094

19 Typical Experimental Details for the Synthesis of (3aR,4S,6S,7aR)-6-[2-(4-Methoxy benzyloxy)ethyl]-2,2-dimethyl-4-vinyltetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran (9) To a stirred solution of iodo compound 20 (520 mg, 1.09 mmol) in THF (5 mL) was added potassium tert-butoxide (122 mg, 1.09 mmol) at 0 °C. The reaction mixture was allowed to stir for 30 min at room temperature. After complete conversion of the starting material (monitored by TLC), it was quenched with water (5 mL) and diluted with ethyl acetate (10 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2 × 10 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate/hexane = 1:9) to afford olefin compound 9 (327 mg, 86%) as a colorless liquid. [α]_D ²⁵ –15.2 (c 0.6, CHCl₃). IR (CHCl₃): ν_max = 3012, 2841, 1832, 1642, 1524, 1507, 1348, 1245, 1179, 1035, 854, 716 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.25 (d, J = 8.7 Hz, 2 H), 6.87 (d, J = 8.7 Hz, 2 H), 5.88 (ddd, J = 17.4, 10.7, 5.1 Hz, 1 H), 5.34 (dt, J = 17.4, 1.6 Hz, 2 H), 4.43 (q, J = 14.8, 3.3 Hz, 2 H), 4.32–4.25 (m, 2 H), 3.97 (t, J = 5.9 Hz, 1 H), 3.88 (m, 1 H), 3.80 (s, 3 H), 3.62–3.51 (m, 2 H), 2.02–1.91 (m, 2 H), 1.77 (m, 1 H), 1.69 (m, 1 H), 1.51 (s, 3 H), 1.35 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 159.1, 136.0, 130.5, 129.2, 117.0, 113.7, 108.5, 75.1, 72.6, 72.2, 71.4, 66.6, 66.3, 55.2, 35.2, 33.2, 27.9, 25.7 ppm. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₂₀H₂₈O₅Na: 371.1834; found: 371.1837
20 Alcaraz L, Mioskowski C, Le Gall T, Shin D.-S, Falck JR. Tetrahedron Lett. 1994; 35: 5449
21 Horita K, Yoshioka T, Tanaka YO, Yonemitsu O. Tetrahedron 1986; 42: 3021

22a Dess DB, Martin JC. J. Org. Chem. 1983; 48: 4155
22b Dess DB, Martin JC. J. Am. Chem. Soc. 1991; 113: 7277

23a Still WC, Gennari C. Tetrahedron Lett. 1983; 24: 4405
23b Janickia I, Kiełbasiński P. Adv. Synth. Catal. 2020; 362: 2552

24 Typical Experimental Details for the Synthesis of (S,2Z,4E)-7-(Methoxymethoxy)nona-2,4,8-trienoic Acid (7) To a stirred solution of ester 25 (300 mg, 1.32 mmol) in 1:1 THF/MeOH (6 mL) was added LiOH·H₂O (557 mg, 13.2 mmol) at 0 °C. The reaction mixture was allowed to stir for 12 h at room temperature. After complete consumption of the starting material (monitored by TLC), the mixture was acidified with 1.0 N HCl and diluted with ethyl acetate (10 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2 × 10 mL). The combined organic layers were washed with saturated aqueous NaHCO₃ (15 mL), dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate/hexane = 2:3) to afford the acid compound 7 (251 mg, 89%) as a colorless liquid. [α]_D ²⁵ –3.1 (c 1.2, CHCl₃). IR (CHCl₃): ν_max = 3292, 2924, 2853, 1689, 1638, 1441, 1229, 1151, 1024, 964, 918, 826, 665 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.42 (m, 1 H), 6.66 (t, J = 11.5 Hz, 1 H), 6.13 (m, 1 H), 5.71 (ddd, J = 17.5, 10.3, 7.5 Hz, 1 H), 5.62 (d, J = 11.4 Hz, 1 H), 5.28–5.21 (m, 2 H), 4.71 (d, J = 6.8 Hz, 1 H), 4.56 (d, J = 6.8 Hz, 1 H), 4.13 (dd, J = 13.3, 6.8 Hz, 1 H), 3.37 (s, 3 H), 2.62–2.42 (m, 2 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 171.6, 147.0, 141.6, 137.4, 129.1, 117.8, 115.5, 93.8, 76.4, 55.5, 39.0 ppm. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₁₁H₁₆O₄Na: 235.0946; found: 235.0954.

25a Garber SB, Kingsbury JS, Gray BL, Hoveyda AH. J. Am. Chem. Soc. 2000; 122: 8168
25b Chatterjee AK, Sanders DP, Grubbs RH. Org. Lett. 2002; 4: 1939
25c Chatterjee AK, Choi TL, Sanders DP, Grubbs RH. J. Am. Chem. Soc. 2003; 125: 11360

26a Nagasawa T, Kuwahara S. Org. Lett. 2013; 15: 3002
26b Stork G, Zhao K. Tetrahedron Lett. 1989; 30: 2173

27a Shiina I, Kubota M, Oshiumi H, Hashizume M. J. Org. Chem. 2004; 69: 1822
27b Schmidt B, Kunz O, Petersen MH. J. Org. Chem. 2012; 77: 10897

28a Li P, Li J, Arikan F, Ahlbrecht W, Dieckmann M, Menche D. J. Am. Chem. Soc. 2009; 131: 11678
28b Menche D, Hassfeld J, Li J, Rudolph S. J. Am. Chem. Soc. 2007; 129: 6100
28c Menche D, Hassfeld J, Li J, Mayer K, Rudolph S. J. Org. Chem. 2009; 74: 7220
28d Li P, Li J, Arikan F, Ahlbrecht W, Dieckmann M, Menche D. J. Org. Chem. 2010; 75: 2429

29 Typical Experimental Details for the Synthesis of (1S,2E,7R,10Z,12E,15S,16E,18Z,21S,23R,24R)-15,23,24-Trihydroxy-7-methyl-8,25-dioxa-bicyclo[19.3.1]pentacosa-2,10,12,16,18-pentaen-9-one (2E-4) To a stirred solution of cyclic compound 29 (5.0 mg, 0.009 mmol) in MeOH (2 mL) was added 4.0 N HCl (0.3 mL) at 0 °C. The reaction mixture was allowed to stir for 24 h at room temperature. After complete consumption of the starting material (monitored by TLC), it was quenched with saturated aqueous NaHCO₃ (2 mL) solution. MeOH solvent was removed under reduced pressure, and the aqueous layer was extracted with ethyl acetate (3 × 5 mL). The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate/hexane = 1:1) to afford macrolactin 3 (2E-4, 3.04 mg, 73%) as an amorphous solid. [α]_D ²⁵ –93.6 (c 0.09, CH₃OH). IR (CHCl₃): ν_max = 3264, 3172, 3014, 2982, 1643, 1604, 1546, 1517, 1447, 1364, 1226, 1143, 1042, 1037, 812, 721 cm^–1. ¹H NMR (500 MHz, CD₃OD): δ = 7.19 (dd, J = 15.3, 10.9 Hz, 1 H), 6.44 (dd, J = 15.2, 10.3 Hz, 1 H), 6.21 (dd, J = 15.1, 10.9 Hz, 1 H), 6.03 (ddd, J = 15.1, 8.3, 6.8 Hz, 1 H), 6.07 (t, J = 10.3 Hz, 1 H), 5.77 (d, J = 15.3 Hz, 1 H), 5.73 (m, 1 H), 5.58 (dd, J = 15.2, 6.9 Hz, 1 H), 5.55 (m, 1 H), 5.50 (dt, J = 10.3, 7.2 Hz, 1 H), 4.95 (m, 1 H), 4.35 (br, 1 H), 4.28 (m, 1 H), 3.81 (ddd, J = 11.4, 4.9, 3.0 Hz, 1 H), 3.69 (t, J = 3.0 Hz, 1 H), 3.50 (m, 1 H), 2.57 (m, 1 H), 2.51 (m, 1 H), 2.39 (m, 1 H), 2.17 (m, 1 H), 2.06 (m, 2 H), 1.72 (m, 2 H), 1.62 (m, 2 H), 1.42 (m, 2 H), 1.24 (d, J = 6.3 Hz, 3 H) ppm. ¹³C{¹H} (150 MHz, CD₃OD): δ = 168.9, 146.7, 141.5, 137.3, 136.0, 132.7, 131.2, 128.3, 127.5, 127.4, 121.3, 81.0, 73.5, 72.6, 72.3, 72.0, 67.4, 41.7, 37.3, 35.8, 35.7, 33.8, 26.7, 21.2 ppm. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₂₄H₃₄O₆Na: 441.2253; found: 441.2248.

Zusatzmaterial

Supporting Information