A Simple Approach for the Synthesis of Thio-, Dithio- and Selenothiocarbamate-Tethered Peptidomimetics

H. S. Lalithamba; T. M. Vishwanatha; M. Samarasimha Reddy; Vommina V. Sureshbabu

doi:10.1055/s-0031-1290683

Synlett, Inhaltsverzeichnis

Synlett 2012; 23(10): 1516-1522
DOI: 10.1055/s-0031-1290683

letter

A Simple Approach for the Synthesis of Thio-, Dithio- and Selenothiocarbamate-Tethered Peptidomimetics

H. S. Lalithamba

#109, Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus, Bangalore University, Dr. B. R. Ambedkar Veedhi, Bangalore 560001, India, eMail: hariccb@hotmail.com eMail: hariccb@gmail.com

,

T. M. Vishwanatha

#109, Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus, Bangalore University, Dr. B. R. Ambedkar Veedhi, Bangalore 560001, India, eMail: hariccb@hotmail.com eMail: hariccb@gmail.com

,

M. Samarasimha Reddy

#109, Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus, Bangalore University, Dr. B. R. Ambedkar Veedhi, Bangalore 560001, India, eMail: hariccb@hotmail.com eMail: hariccb@gmail.com

,

Vommina V. Sureshbabu*

#109, Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus, Bangalore University, Dr. B. R. Ambedkar Veedhi, Bangalore 560001, India, eMail: hariccb@hotmail.com eMail: hariccb@gmail.com

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Abstract

A simple and efficient method is described for the synthesis of thio-, dithio- and selenothiocarbamate-linked peptidomimetics. The nucleophilic addition of enantiopure N ^α-protected amino alkyl thiols to isocyanates, isothiocyanates or isoselenocyanates obtained from amino acid esters proceeds smoothly in the presence of catalytic amount of DMAP. The protocol was further extended for the synthesis of N,N′-orthogonally protected thio-, dithio- and selenothiocarbamate-linked peptidomimetics. The reaction is mild, free from racemization, and the products were obtained in good yield.

Key words

peptidomimetics - isocyanates - isothiocyanates and isoselenocyanates - amino alkyl thiols - thiocarbamates - dithiocarbamates - selenothiocarbamates

Volltext

Referenzen

References

1a Conradi RA, Hilgers AR, Ho NF. H, Burton PS. Pharm. Res. 1992; 9: 435
1b Pseudo-Peptides in Drug Discovery. Nielsen PE. Wiley-VCH; Weinheim: 2004
1c Peptides: Chemistry and Biology. Sewald N, Jakubke H.-D. Wiley-VCH; Weinheim: 2002: 354

2a Synthesis of Peptides and Peptidomimetics (Houben-Weyl). Vol. E22c. Goodman M, Felix A, Moroder L, Toniolo C. Georg Thieme; Stuttgart: 2003. ; and references cited therein
2b Boeijen A, van Ameijde J, Liskamp RM. J. J. Org. Chem. 2001; 66: 8454

3a Cho CY, Moran EJ, Cherry SR, Stephans JC, Fodor SP, Adams CL, Sundaram A, Jacobs JW, Schultz PG. Science 1993; 261: 1303
3b Liskamp RM. J. Angew. Chem., Int. Ed. Engl. 1994; 33: 633

4a Cho CY, Liu CW, Wemmer DE, Schultz PG. Bioorg. Med. Chem. Lett. 1999; 7: 1171
4b Warrass R, Walden P, Wiesmuller K.-H, Jung G. Lett. Pept. Sci. 1998; 5: 125

5 Wang X, Huq I, Rana TM. J. Am. Chem. Soc. 1997; 119: 6444

6a Sharma AK, Sharma A, Desai D, Madhunapantula SV, Huh SJ, Robertson GP, Amin S. J. Med. Chem. 2008; 51: 7820
6b Zheng G.-Q, Kenney PM, Lam LK. T. J. Med. Chem. 1992; 35: 185
6c Bardajee GR, Sadraei S, Taimoory S, Abtin E. Asian J. Biochem Pharma. Res. 2011; 1: 2331
6d Ronconi L, Marzano C, Zanello P, Corsini M, Miolo G, Macca C, Trevisan A, Fregona D. J. Med. Chem. 2006; 49: 1648
6e Elgemeie GH, Sayed SH. Synthesis 2001; 1747

7 Hou X, Ge Z, Wang T, Guo W, Cui J, Cheng T, Lai C, Li R. Bioorg. Med. Chem. Lett. 2006; 16: 4214

8a Ronconi L, Marzano C, Zanello P, Corsini M, Miolo G, Macca C, Trevisan A, Fregona D. J. Med. Chem. 2006; 49: 1648
8b Len C, Postel D, Ronco G, Villa P, Goubert C, Jeufrault E, Mathon B, Simon H. J. Agric. Food. Chem. 1997; 45: 3
8c Cao S.-L, Feng Y.-P, Jiang Y.-Y, Liu S.-Y, Ding G.-Y, Li R.-T. Bioorg. Med. Chem. Lett. 2005; 15: 1915
8d Nogueira CW, Zeni G, Rocha JB.T. Chem. Rev. 2004; 104: 6255
8e Klayman DL, Gunther WH. H In Organic Selenium Compounds: Their Chemistry and Biology. Wiley; New York: 1973: 30
8f Nicolaou KC, Petasis NA In Selenium in Natural Products Synthesis. CIS Inc; Philadelphia: 1984. Chap. 3

9 Goel A, Mazur SJ, Fattah RJ, Hartman TL, Turpin JA, Huang M, Rice WG, Appella E, Inman JK. Bioorg. Med. Chem. Lett. 2002; 12: 767

10a Morf P, Raimondi F, Nothofer H.-G, Schnyder B, Yasuda A, Wessels JM, Jung TA. Langmuir 2006; 22: 658
10b Bongar BP, Sadavarte VS, Uppalla LS. J. Chem. Res. 2004; 9: 450
10c Greene TW, Wuts PG. M. Protective Groups in Organic Synthesis. 3rd ed Wiley; New York: 1999: 484-486

11 Mugesh G, du Mont W.-W, Helmut S. Chem. Rev. 2001; 101: 2125
12 Organoselenium Chemistry: A Practical Approach. Liotta D. Oxford University Press; Oxford: 1999

13a Mizuno T, Nishiguchi I, Sonoda N. Tetrahedron 1994; 50: 5669
13b Tilles H. J. Am. Chem. Soc. 1959; 81: 714
13c Mizuno T, Nishiguchi I, Okushi T, Hireashima T. Tetrahedron Lett. 1991; 32: 6867
13d Copeland CM, Ghosh J, McAdam DP, Skelto BW, Stick RV, White AH. Aust. J. Chem. 1988; 41: 549
13e Koketsu M, Fukuta Y, Ishihara H. J. Org. Chem. 2002; 67: 1008
13f Azizi N, Aryanasab F, Saidi MR. Org. Lett. 2006; 8: 5275
13g Watkins BE, Rapoport H. J. Org. Chem. 1982; 47: 4471

14a Yamaguchi T, Harada N, Ozaki K, Hayashi M, Arakawa H, Hashiyama T. Tetrahedron 1999; 55: 1005
14b McCarthy WC, Foss LE. J. Org. Chem. 1977; 42: 1508
14c Vermeulen M, Zwanenburg B, Chittenden GJ. F, Verhagen H. Eur. J. Med. Chem. 2003; 38: 729

15 Wood MR, Duncalf DJ, Rannard SP, Perrier S. Org. Lett. 2006; 8: 553 ; and references cited therein

16a Walter W, Bode KD. Angew. Chem., Int. Ed. Engl. 1967; 6: 281
16b Garin J, Melandz E, Merchain FL, Tejero T, Urid S, Ayestaron J. Synthesis 1991; 147
16c Xia S, Wang X, Ge Z.-M, Cheng T.-M, Li R.-T. Tetrahedron 2009; 65: 1005
16d Ranu BC, Saha A, Banerjee S. Eur. J. Org. Chem. 2008; 519
16e Len C, Boulogne-Merlot A.-S, Postel D, Ronco G, Villa P. J. Agric. Food Chem. 1996; 44: 2856

17a Koketsu M, Fukuta Y, Ishihara H. J. Org. Chem. 2002; 67: 1008
17b Koketsu M, Otsuka T, Ishihara H. Phosphorus, Sulfur Silicon Relat. Elem. 2004; 178: 443

18 Hemantha HP, Sureshbabu VV. Tetrahedron Lett. 2009; 50: 7062
19 Sureshbabu VV, Narendra N, Nagendra G. J. Org. Chem. 2009; 74: 153

20a Patil BS, Vasanthakumar GR, Sureshbabu VV. J. Org. Chem. 2003; 68: 7274
20b Sureshbabu VV, Patil BS, Ramanarao RV. J. Org. Chem. 2006; 71: 7697

21 Sureshbabu VV, Naik SA, Hemantha HP, Narendra N, Das U, Guru Row TN. J. Org. Chem. 2009; 74: 5260

22a Hemantha HP, Sureshbabu VV. J. Pept. Sci. 2010; 16: 644
22b Chennakrishnareddy G, Nagendra G, Hemantha HP, Das U, Guru Row TN, Sureshbabu VV. Tetrahedron 2010; 66: 6718

23 Sureshbabu VV, Vishwanatha TM, Vasantha B. Synlett 2010; 1037
24 General Procedure for the Synthesis of Thio-, Dithio- and Selenothiocarbamate-Linked Peptidomimetics: To a solution of PgNH-CHR-ψ-[CH₂SH] (10.0 mmol) in anhyd CH₂Cl₂ (10.0 mL), isocyanato derivatives (10.0 mmol) and DMAP (0.2 equiv) were added. The reaction mixture was stirred for 30–50 min at r.t. After the completion of the reaction (TLC), the organic layer was washed with H₂O (10 mL), brine (10 mL) and dried over Na₂SO₄. The organic phase was evaporated under vacuo and the crude was recrystallized (Et₂O–THF) or purified through column chromatography using EtOAc–n-hexane (20:80) as eluent. Spectral data for compounds: Compound 5a: ¹H NMR (300 MHz, CDCl₃): δ = 0.98 (d, 6 H, J = 6.1 Hz), 1.59 (d, 3 H, J = 5.5 Hz), 2.90–3.11 (m, 3 H), 3.60 (s, 3 H), 3.91 (m, 1 H), 4.28 (m, 1 H), 4.20 (t, 1 H, J = 4.6 Hz), 5.01 (d, 2 H, J = 5.1 Hz), 5.16 (br, 2 H), 7.22–7.77 (m, 8 H). ¹³C NMR (100 MHz, CDCl₃): δ = 19.6, 20.1, 30.9, 37.4, 45.7, 47.1, 51.9, 58.3, 66.6, 126.8, 127.3, 128.2, 128.9, 141.4, 143.2, 155.7, 164.5, 171.8. HRMS: m/z [M + Na]⁺ calcd for C₂₅H₃₀N₂O₅S: 493.1773; found: 493.1775. Compound 5b: ¹H NMR (300 MHz, CDCl₃): δ = 2.70–3.02 (m, 2 H), 3.21–3.30 (m, 4 H), 3.62 (s, 3 H), 4.20 (m, 1 H), 4.83 (m, 1 H), 5.16 (br, 2 H), 5.32 (s, 2 H), 7.19–7.25 (m, 15 H). ¹³C NMR (100 MHz, CDCl₃): δ = 34.1, 36.2, 43.3, 52.3, 53.1, 56.5, 64.3, 126.1, 126.3, 126.8, 127.0, 127.2, 127.4, 127.8, 128.2, 129.0, 138.1, 139.0, 140.1, 155.2, 164.2, 171.7. HRMS: m/z [M + Na]⁺ calcd for C₂₈H₃₀N₂O₅S: 529.1773; found: 529.1770. Compound 5c: ¹H NMR (300 MHz, CDCl₃): δ = 0.94 (t, 3 H, J = 6.0 Hz), 1.02 (d, 3 H, J = 5.7 Hz), 1.22 (m, 2 H), 2.24 (m, 1 H), 2.92–3.24 (m, 4 H), 3.61 (s, 3 H), 3.75 (m, 2 H), 3.78 (m, 1 H), 4.81 (m, 1 H), 5.18 (br, 2 H), 5.32 (s, 2 H), 7.18–7.20 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 12.1, 15.0, 24.1, 32.2, 33.3, 39.0, 40.0, 52.1, 53.9, 55.7, 65.4, 126.4, 127.2, 128.1, 128.3, 128.5, 128.9, 137.4, 141.3, 155.8, 165.2, 171.8. HRMS: m/z [M + Na]⁺ calcd for C₂₆H₃₄N₂O₅S₂: 541.1807; found: 541.1805. Compound 5d: ¹H NMR (300 MHz, CDCl₃): δ = 2.20–2.30 (m, 4 H), 3.13 (d, 2 H, J = 5.2 Hz), 3.43–3.60 (m, 3 H), 3.63 (s, 3 H), 4.20 (t, 1 H, J = 3.5 Hz), 4.91 (d, 2 H, J = 5.8 Hz), 5.15 (br, 2 H), 5.21 (s, 2 H), 7.19–7.72 (m, 13 H). ¹³C NMR (100 MHz, CDCl₃): δ = 25.2, 28.3, 37.4, 40.6, 47.2, 51.8, 55.2, 68.1, 68.9, 126.2, 126.9, 127.5, 128.0, 128.4, 128.6, 129.0, 141.2, 143.2, 157.0, 171.1, 173.2, 196.2. HRMS: m/z [M + Na]⁺ calcd for C₃₁H₃₂N₂O₆S₂: 615.1599; found: 615.1595. Compound 5e: ¹H NMR (300 MHz, CDCl₃): δ = 0.90 (d, 6 H, J = 6.3 Hz), 1.25 (d, 3 H, J = 5.8 Hz), 1.70–1.75 (m, 3 H), 2.12–3.20 (m, 2 H), 3.63 (s, 3 H), 3.66 (m, 1 H), 3.85 (m, 1 H), 4.28 (t, 1 H, J = 4.8 Hz), 4.91 (d, 2 H, J = 6.7 Hz), 5.15 (br, 2 H), 7.26–7.78 (m, 8 H). ¹³C NMR (100 MHz, CDCl₃): δ = 18.5, 19.6, 20.7, 40.5, 43.8, 47.0, 47.5, 50.9, 52.4, 66.0, 126.7, 127.5, 128.0, 128.6, 141.4, 143.2, 154.7, 173.2, 195.7. HRMS: m/z [M + Na]⁺ calcd for C₂₆H₃₂N₂O₄S₂: 523.1701; found: 523.1705. Compound 5f: ¹H NMR (300 MHz, CDCl₃): δ = 0.95 (d, 6 H, J = 5.2 Hz), 2.15 (s, 3 H), 2.23–2.47 (m, 5 H), 2.95 (d, 2 H, J = 5.8 Hz), 3.45 (m, 1 H), 3.62 (s, 3 H), 3.86 (m, 1 H), 5.17 (br, 2 H), 5.22 (s, 2 H), 7.19–7.22 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 16.2, 17.3, 17.5, 29.0, 31.1, 33.2, 36.5, 52.1, 56.2, 58.4, 65.4, 126.1, 127.6, 128.3, 142.1, 155.7, 171.2, 197.0. HRMS: m/z [M + Na]⁺ calcd for C₂₀H₃₀N₂O₄S₃: 481.1265; found: 481.1261. Compound 5g: ¹H NMR (300 MHz, CDCl₃): δ = 1.33 (d, 3 H, J = 4.6 Hz), 2.96–3.02 (m, 2 H), 3.04–3.31 (m, 2 H), 3.50 (s, 3 H), 3.81 (m, 1 H), 4.10 (m, 1 H), 4.12 (t, 1 H, J = 4.9 Hz), 4.99 (d, 2 H, J = 6.4 Hz), 5.22 (br, 2 H), 7.12–7.81 (m, 13 H). ¹³C NMR (100 MHz, CDCl₃): δ = 19.1, 36.2, 37.1, 47.2, 48.2, 52.0, 58.7, 67.2, 125.1, 126.7, 127.5, 127.9, 128.0, 128.2, 128.6, 139.0, 141.1, 143.4, 155.7, 171.2, 205.7. ⁷⁷Se NMR (76 MHz, Me₂Se–CDCl₃): δ = 322.0. HRMS: m/z [M + Na]⁺ calcd for C₂₉H₃₀N₂O₄SSe: 605.0989; found: 605.0984. Compound 5h: ¹H NMR (300 MHz, CDCl₃): δ = 0.95 (d, 6 H, J = 5.6 Hz), 2.30 (m, 1 H), 2.73–2.95 (m, 2 H), 2.98–3.21 (m, 2 H), 3.61 (s, 3 H), 3.80 (m, 1 H), 4.10 (m, 1 H), 4.21 (t, 1 H, J = 4.2 Hz), 4.80 (d, 2 H, J = 6.4 Hz), 5.21 (br, 2 H), 5.30 (s, 2 H), 7.12–7.81 (m, 13 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.2, 17.4, 32.9, 34.3, 37.4, 47.2, 51.8, 52.1, 58.3, 67.1, 69.2, 125.3, 126.2, 127.2, 127.3, 128.0, 128.3, 128.6, 141.3, 142.1, 143.7, 155.1, 171.2, 173.2, 203.4. ⁷⁷Se NMR (76 MHz, Me₂Se–CDCl₃): δ = 322.0. HRMS: m/z [M + Na]⁺ calcd for C₃₃H₃₆N₂O₆SSe: 691.1357; found: 691.1352. Compound 5i: ¹H NMR (300 MHz, CDCl₃): δ = 0.94 (t, 3 H, J = 5.8 Hz), 1.01 (d, 3 H, J = 6.1 Hz), 1.37 (m, 2 H), 2.51 (m, 1 H), 2.60–2.81 (m, 2 H), 2.94–3.23 (m, 2 H), 3.41 (m, 1 H), 3.59 (s, 3 H), 4.21 (m, 1 H), 5.19 (br, 2 H), 5.29 (s, 2 H), 7.12–7.20 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 12.2, 15.2, 36.2, 37.1, 42.2, 51.2, 55.3, 58.9, 66.3, 125.4, 126.5, 127.4, 128.0, 128.3, 128.7, 139.1, 141.4, 155.2, 171.3, 202.4. ⁷⁷Se NMR (76 MHz, Me₂Se–CDCl₃): δ = 322.0. HRMS: m/z [M + Na]⁺ calcd for C₂₅H₃₂N₂O₄SSe: 559.1146; found: 559.1149. Compound 7a: ¹H NMR (300 MHz, CDCl₃): δ = 0.97 (d, 6 H, J = 6.0 Hz), 1.31 (d, 3 H, J = 5.4 Hz), 1.43 (m, 2 H), 1.76 (m, 1 H), 2.90–3.21 (m, 2 H), 3.01–3.35 (m, 2 H), 4.01–4.21 (m, 2 H), 4.25 (t, 1 H, J = 4.0 Hz), 5.01 (d, 2 H, J = 7.2 Hz), 5.31 (s, 2 H), 5.88 (br, 3 H), 7.19–7.82 (m, 13 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.2, 22.1, 23.4, 37.5, 42.2, 45.2, 47.0, 47.8, 48.9, 65.2, 67.2, 127.2, 127.4, 127.8, 128.1, 128.5, 128.8, 129.4, 141.2, 141.5, 143.1, 155.7, 163.1. HRMS: m/z [M + Na]⁺ calcd for C₃₃H₃₉N₃O₅S: 612.2508; found: 612.2505. Compound 7b: ¹H NMR (300 MHz, CDCl₃): δ = 1.21 (d, 3 H, J = 6.6 Hz), 1.25–1.60 (m, 6 H), 2.90–3.20 (m, 4 H), 3.25–3.45 (m, 2 H), 3.75 (m, 1 H), 5.01 (m, 1 H), 4.23 (t, 1 H, J = 4.5 Hz), 5.21 (d, 2 H, J = 6.1 Hz), 5.32 (s, 4 H), 5.81 (br, 4 H), 7.16–7.79 (m, 18 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.7, 22.4, 29.2, 33.8, 35.0, 47.1, 47.4, 49.2, 49.4, 49.8, 67.4, 68.2, 68.5, 126.1, 126.3, 126.9, 127.2, 127.4, 127.7, 128.2, 128.6, 128.9, 129.4, 141.1, 141.4, 141.8, 143.4, 155.3, 155.7, 156.2, 167.5. HRMS: m/z [M + Na]⁺ calcd for C₄₁H₄₆N₄O₇S: 761.2985; found: 761.2980. Compound 7c: ¹H NMR (300 MHz, CDCl₃): δ = 1.02 (d, 6 H, J = 5.2 Hz), 1.49 (m, 2 H), 1.81 (m, 1 H), 3.01–3.32 (m, 4 H), 3.69 (m, 2 H), 4.32 (m, 1 H), 4.31 (t, 1 H, J = 5.2 Hz), 4.83 (d, 2 H, J = 6.2 Hz), 5.32 (s, 2 H), 5.80 (br, 3 H), 7.19–7.81 (m, 13 H). ¹³C NMR (100 MHz, CDCl₃): δ = 22.1, 22.4, 23.3, 32.5, 39.0, 41.7, 46.3, 47.2, 47.5, 64.2, 68.2, 126.2, 127.6, 127.3, 128.2, 128.7, 128.9, 129.4, 141.3, 141.8, 143.5, 155.2, 156.3, 169.1. HRMS: m/z [M + Na]⁺ calcd for C₃₂H₃₇N₃O₅S: 598.2352; found: 598.2350. Compound 7d: ¹H NMR (300 MHz, CDCl₃): δ = 0.95 (d, 6 H, J = 5.6 Hz), 1.20 (s, 9 H), 1.72 (m, 3 H), 2.40–2.49 (m, 4 H), 2.51 (d, 2 H, J = 4.9 Hz), 3.48 (m, 1 H), 3.99 (m, 1 H), 4.22 (t, 1 H, J = 4.2 Hz), 4.91 (d, 2 H, J = 6.7 Hz), 5.92 (br, 3 H), 7.21–7.78 (m, 13 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.1, 22.9, 27.7, 38.4, 40.1, 41.6, 46.9, 47.8, 49.1, 51.5, 65.7, 82.3, 127.5, 127.8, 127.9, 128.2, 128.6, 128.9, 129.5, 141.7, 142.3, 143.4, 155.6, 156.3, 194.5. HRMS: m/z [M + Na]⁺ calcd for C₃₆H₄₅N₃O₄S₂: 670.2749; found: 670.2745. Compound 7e: ¹H NMR (300 MHz, CDCl₃): δ = 0.99 (d, 6 H, J = 5.6 Hz), 1.40 (m, 2 H), 1.80 (m, 1 H), 2.74–3.10 (m, 6 H), 3.80 (m, 1 H), 4.19 (m, 1 H), 4.35 (t, 1 H, J = 4.2 Hz), 4.87 (d, 2 H, J = 6.7 Hz), 5.33 (s, 2 H), 5.82 (br, 3 H), 7.23–7.81 (m, 18 H). ¹³C NMR (100 MHz, CDCl₃): δ = 22.1, 23.1, 23.3, 39.4, 41.9, 42.3, 47.0, 47.8, 49.5, 55.5, 65.1, 67.4, 126.5, 126.8, 127.1, 127.5, 127.9, 128.2, 128.5, 128.7, 129.5, 139.2, 141.2, 143.3, 155.2, 155.8, 198.4. HRMS: m/z [M + Na]⁺ calcd for C₃₉H₄₃N₃O₄S₂: 704.2593; found: 704.2595. Compound 7f: ¹H NMR (300 MHz, CDCl₃): δ = 0.91 (t, 3 H, J = 5.6 Hz), 1.08 (d, 3 H, J = 5.1 Hz), 1.32 (m, 2 H), 2.23 (m, 1 H), 2.81–3.32 (m, 6 H), 3.80 (m, 1 H), 4.37 (t, 1 H, J = 5.2 Hz), 4.99 (d, 2 H, J = 6.7 Hz), 5.30 (s, 2 H), 5.82 (br, 3 H), 7.20–7.78 (m, 13 H). ¹³C NMR (100 MHz, CDCl₃): δ = 12.2, 16.1, 25.5, 35.3, 40.2, 41.0, 43.2, 47.1, 54.2, 66.1, 68.4, 126.6, 127.4, 127.8, 128.5, 128.7, 129.0, 129.5, 141.0, 141.5, 144.3, 155.6, 156.0, 198.4. HRMS: m/z [M + Na]⁺ calcd for C₃₂H₃₇N₃O₄S₂: 614.2123; found: 614.2126. Compound 7g: ¹H NMR (300 MHz, CDCl₃): δ = 0.97 (d, 6 H, J = 5.4 Hz), 1.31 (d, 3 H, J = 5.8 Hz), 1.12 (s, 9 H), 2.40 (m, 1 H), 2.74–2.99 (m, 2 H), 3.04–3.22 (m, 2 H), 3.81–4.01 (m, 2 H), 5.01 (s, 2 H), 6.02 (br, 3 H), 7.10–7.26 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.2, 19.2, 29.0, 31.2, 39.1, 47.2, 48.2, 59.1, 65.2, 79.2, 127.5, 127.8, 128.2, 141.2, 155.7, 204.2. ⁷⁷Se NMR (76 MHz, Me₂Se–CDCl₃): δ = 320.0. HRMS: m/z [M + Na]⁺ calcd for C₂₂H₃₅N₃O₄SSe: 540.1411; found: 540.1416. Compound 7h: ¹H NMR (300 MHz, CDCl₃): δ = 0.95 (t, 3 H, J = 5.5 Hz), 0.99 (d, 3 H, J = 5.6 Hz), 1.10 (s, 9 H), 1.25 (m, 2 H), 1.32 (d, 3 H, J = 5.2 Hz), 2.12–3.32 (m, 5 H), 3.90 (m, 2 H), 4.30 (t, 1 H, J = 4.2 Hz), 4.92 (d, 2 H, J = 5.5 Hz), 5.69 (br, 3 H), 7.21–7.76 (m, 8 H). ¹³C NMR (100 MHz, CDCl₃): δ = 11.0, 14.3, 18.8, 26.5, 28.6, 32.1, 40.2, 48.1, 49.1, 52.3, 57.5, 68.2, 80.4, 126.0, 127.1, 127.8, 128.3, 141.3, 143.7, 155.1, 155.7, 202.3. ⁷⁷Se NMR (76 MHz, Me₂Se–CDCl₃): δ = 320.0. HRMS: m/z [M + Na]⁺ calcd for C₃₀H₄₁N₃O₄SSe: 642.1881; found: 642.1884. Compound 7i: ¹H NMR (300 MHz, CDCl₃): δ = 0.98 (d, 6 H, J = 6.5 Hz), 2.40 (m, 1 H), 2.60–3.22 (m, 6 H), 3.87 (m, 1 H), 4.30 (m, 1 H), 4.33 (t, 1 H, J = 4.3 Hz), 4.92 (d, 2 H, J = 6.6 Hz), 5.33 (s, 2 H), 5.99 (br, 3 H), 7.21–7.76 (m, 18 H). ¹³C NMR (100 MHz, CDCl₃): δ = 16.9, 32.8, 34.5, 40.9, 47.5, 49.6, 53.2, 59.9, 64.3, 68.4, 126.3, 126.8, 126.9, 127.0, 127.3, 127.9, 128.1, 128.3, 128.7, 129.0, 139.2, 140.3, 141.3, 143.9, 155.2, 155.9, 201.5. ⁷⁷Se NMR (76 MHz, Me₂Se–CDCl₃): δ = 320.0. HRMS: m/z [M + Na]⁺ calcd for C₃₈H₄₁N₃O₄SSe: 738.1881; found: 738.1884