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DOI: 10.1055/s-0029-1219205
The Total Synthesis of Trungapeptin A
Publication History
Publication Date:
15 January 2010 (online)
![](https://www.thieme-connect.de/media/synlett/201003/lookinside/thumbnails/10.1055-s-0029-1219205-1.jpg)
Abstract
Trungapeptin A, a novel cyclodepsipeptide isolated from a marine cyanobacterium (Lyngbya majuscula), has been synthesised and its structure unambiguously confirmed.
Key words
marine cyanobacterium - Lyngbya majuscule - cyclodepsipeptide - total synthesis - lactamisation
- 1
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References and Notes
All new compounds gave spectroscopic
data in agreement with the assigned structures. Data for compound 13: [α]D
²²
-63.2
(c 0.5, MeOH). R
f
= 0.4
(cyclohexane-EtOAc, 5:5). ¹H NMR (300 MHz,
CDCl3): δ = 0.11 (s, 6 H,
SiMe2), 0.05 (s, 9 H, SiMe3), 0.79-0.95
(m, 18 H, CH3 Val, CH3 NMeVal, CH3 alloIle),
0.95 (s, 9 H, SitBu), 0.95-1.39
(m, 7 H, CH2Si, CH3, CH2 alloIle), 1.40-1.62 (m, 4 H,
CH2CH2, H-4, H-5), 1.90-2.22 (m,
9 H, CHβ NMeVal, CHβ Val,
CHβ alloIle, CH2 Pro, ≡CH,
CH2, H-6), 2.35-2.40 (m, 1 H, CH2 Pro), 2.47-2.52
(m, 1 H, CH, H-2), 3.03 (s, 3 H, NMe), 3.06-3.08 (m,
2 H, CH2-Ph), 3.28-3.33 (m, 1 H,
NCH2), 3.58-3.66 (m, 1 H, NCH2),
3.70-3.75 (m, 1 H, CH, H-3), 4.22 (dd, J = 7.1, 8.6
Hz, 2 H, OCH2), 4.55 (dd, J = 4.1,
8.5 Hz, 1 H, CHα alloIle),
4.61-4.64 (m, 2 H, CHα Val,
CHα Pro), 5.08 (d, J = 10.3
Hz, 1 H, CHα NMeVal), 5.19-5.20
(m, 1 H, CHα Pla), 6.93 (d, J = 9.0 Hz,
1 H, NH Val), 7.14 (d, J = 8.4 Hz, 1 H,
NH alloIle), 7.23-7.33 (m, 5 H,
Ar-H). ¹³C NMR (75 MHz, CDCl3): δ = -4.5
(SiMe2), -1.5 (SiMe3), 11.7 (CH3 alloIle), 13.7 (CH3), 14.6
(CH3 alloIle), 17.3 (CH2Si), 18.0
(Cq-tBu), 18.3 (CH2, C-6),
18.4 (CH3 Val), 18.8 (CH3 NMeVal), 19.2 (CH3 Val),
19.5 (CH3 NMeVal), 24.8 (CH2, C-5), 25.2 (CH2 Pro),
25.8 (SitBu), 26.2 (CH2 alloIle), 26.8 (CH2 Pro),
27.3 (CHβ NMeVal), 31.4 (CHβ Val),
31.4 (NMe), 31.6 (CH2, C-4), 37.2 (CH2-Ph),
37.4 (CHβ alloIle), 45.8
(CH, C-2), 47.0 (NCH2 Pro), 53.7 (CHα Val),
55.7 (CHα alloIle),
59.9 (CHα Pro), 60.9 (CHα NMeVal),
63.5 (OCH2), 68.4 (≡CH), 73.3 (CHα Pla),
74.6 (CH, C-3), 84.0 (Cq, C-7), 128.9 (CH), 129.1 (CH), 129.1 (CH),
129.4 (CH), 129.4 (CH), 135.8 (Cq), 168.9 (C=O Pla), 170.5
(C=O NMeVal), 170.6 (C=O Pro), 172.0 (C=O alloIle), 172.8 (C=O Val), 173.9
(C=O, C-1). HRMS: m/z calcd for C51H87N4O9Si2: 955.6012;
found: 955.6008. MALDI-TOF MS (LD+): m/z (%) = 978.1
(100) [M + 23]+
˙
, 811.9 (57), 689.7 (17),
499.5 (47), 381.6 (28).
Unfortunately, we were unable to control this reaction; coupling of Boc-Val-CO-NMe-Val-OH (17) with 7 under Yamaguchi’s conditions often afforded a mixture of diastereoisomers.
14Data for compound 24: [α]D ²5 -81.6 (c 0.5, MeOH). R f = 0.28 (cyclohexane-EtOAc, 7:3). ¹H NMR (300 MHz, CDCl3): δ = 0.03 (s, 9 H, SiMe3), 0.80-1.02 (m, 20 H, CH3 Val, CH3 NMeVal, CH3 alloIle, CH2Si), 1.19-1.21 (m, 4 H, CH3, CH2 alloIle), 1.38-1.62 [m, 12 H, C(CH3)3, CH2 alloIle, CH2, H-5], 1.65-1.75 (m, 2 H, CH2, H-4), 1.80-2.05 (m, 6 H, CHβ Val, CHβ alloIle, CH2-CH2 Pro, ºCH), 2.10-2.20 (m, 3 H, CHβ NMeVal, CH2, H-6), 2.30-2.40 (m, 1 H, CH2 Pro), 2.62-2.67 (m, 1 H, CH, H-2), 2.95-3.10 (m, 5 H, NMe, CH2-Ph), 3.21-3.32 (m, 1 H, NCH2), 3.55-3.62 (m, 1 H, NCH2), 4.15 (dd, J = 7.1, 8.6 Hz, 2 H, OCH2), 4.32-4.36 (m, 1 H, CHα Val), 4.53-4.62 (m, 2 H, CHα alloIle, CHα Pro), 4.95 (d, J = 10.3 Hz, 1 H, CHα NMeVal), 5.15-5.21 (m, 3 H, CHα Pla, CH, H-3, NH Val), 7.15-7.30 (m, 6 H, Ar-H, NH alloIle). ¹³C NMR (75 MHz, CDCl3): δ = -1.5 (SiMe3), 11.7 (CH3 alloIle), 12.5 (CH3), 14.4 (CH3 alloIle), 17.2 (CH2Si), 17.5 (CH3 Val), 18.0 (CH2, C-6), 18.6 (CH3 NMeVal), 19.3 (CH3 Val), 19.6 (CH3 NMeVal), 24.0 (CH2, C-5), 25.2 (CH2 Pro), 26.3 (CH2 alloIle), 26.6 (CH2 Pro), 27.3 (CHβ NMeVal), 28.1 [C(CH3)3], 30.9 (CHβ Val), 30.9 (CH2, C-4), 31.6 (NMe), 37.1 (CH2-Ph), 37.1 (CHβ alloIle), 43.3 (CH, C-2), 47.0 (NCH2 Pro), 55.2 (CHα Val), 55.7 (CHα alloIle), 59.8 (CHα Pro), 61.5 (CHα NMeVal), 62.9 (OCH2), 68.7 (≡CH), 73.2 (CHα Pla), 74.7 (CH, C-3), 79.4 [Cq, C(CH3)3], 83.4 (Cq, C-7), 127.0 (CH), 128.5 (CH), 128.5 (CH), 129.0 (CH), 129.0 (CH), 135.6 (Cq), 155.9 (Cq), 168.9 (C=O Pla), 170.4 (C=O NMeVal), 170.5 (C=O Pro), 171.2 (C=O alloIle), 173.4 (C=O Val), 173.5 (C=O, C-1). HRMS: m/z calcd for C50H80N4O11NaSi: 963.5491; found: 963.5499. MALDI-TOF MS (LD+): m/z (%) = 963.4 (100) [M + 23]+ ˙ , 872.3 (48), 863.4 (23), 575.0(13), 463.6 (18), 447.5 (67).
16Spectroscopic data of synthetic trungapeptin
A (1): [α]D
²²
-45
(c 0.37, MeOH). ¹H
NMR (300 MHz, CDCl3): δ = 0.85 (m,
6 H, CH3 alloIle),
0.92 (d, J = 6.7
Hz, 3 H, CH3 Val), 0.95 (m, 1 H, CH2 Pro),
0.96 (d, J = 6.7
Hz, 3 H, CH3 Val), 1.06 (d, J = 6.5
Hz, 3 H, CH3 NMeVal), 1.12 (m, 1 H,
CH2 alloIle), 1.19 (d, J = 7.1 Hz,
3 H, CH3), 1.31 (m, 1 H, CH2 alloIle), 1.38 (d, J = 6.5
Hz, 3 H, CH3 NMeVal), 1.41 (m, 1 H,
CH2, H-5), 1.45 (m, 1 H, CH2 Pro),
1.52 (m, 1 H, CH2, H-5), 1.70 (m, 1 H,
CH2 Pro), 1.85 (m, 1 H, CH2, H-4),
1.88 (m, 1 H, CHβ alloIle),
1.99 (t, J = 2.4
Hz, 1 H, ≡CH), 1.99 (m, 1 H, CH2,
H-4), 2.05 (m, 1 H, CHβ Val), 2.14
(dd, J = 6.2,
12.5 Hz, 1 H, CH2 Pro), 2.22 (td, J = 2.7, 6.7
Hz, 2 H, CH2, H-6), 2.41 (m, 1 H, CHβ NMeVal),
2.49 (dd, J = 3.3,
7.1 Hz, 1 H, CH, H-2), 2.99 (s, 3 H, NMe), 3.18
(dd, J = 10.7,
12.7 Hz, 1 H, CH2-Ph), 3.30 (d, J = 7.6 Hz,
1 H, CHα Pro), 3.34 (m, 1 H,
CH2Ph), 3.39 (m, 1 H, NCH2 Pro), 3.50
(m, 1 H, NCH2 Pro), 4.25 (t, J = 8.1
Hz, 1 H, CHα alloIle),
4.44 (d, J = 9.6
Hz, 1 H, CHα NMeVal), 4.63 (t, J = 9.5 Hz,
1 H, CHα Val), 4.95 (dt, J = 3.0, 9.9
Hz, 1 H, CH, H-3), 5.06 (dd, J = 5.5,
10.5 Hz, 1 H, CHα Pla), 5.96 (d, J = 9.5 Hz,
1 H, NH Val), 7.24-7.36 (m, 5 H, Ar-H),
7.84 (d, J = 8.3
Hz, 1 H, NH alloIle). ¹³C
NMR (75 MHz, CDCl3):
δ = 11.2
(CH3, alloIle), 12.9 (CH3),
15.4 (CH3, alloIle), 17.9 (CH2,
C-6), 18.7 (CH3 Val), 19.7 (CH3 Val), 20.1
(CH3 NMeVal), 21.3 (CH3 NMeVal), 21.8 (CH2 Pro),
24.3 (CH2, C-5), 26.2 (CH2, alloIle),
28.7 (CH2, C-4), 29.5 (CHβ NMeVal),
30.5 (NMe), 30.6 (CH2 Pro), 31.7 (CHβ Val),
35.0 (CHβ alloIle),
38.2 (CH2-Ph), 43.2 (CH, C-2), 46.5 (NCH2 Pro),
53.7 (CHα Val), 57.3 (CHα alloIle), 61.0 (CHα Pro), 65.5
(CHα NMeVal), 69.3 (≡CH), 74.7 (CH,
C-3), 75.0 (CHα Pla), 83.7 (Cq, C-7), 127.9
(CH), 129.2 (CH), 129.8 (CH), 134.2 (Cq), 169.1 (C=O Pla),
170.3 (C=O, alloIle), 170.4 (C=O
Pro), 171.8 (C=O NMeVal), 172.8 (C=O, C-1), 173.6 (C=O
Val). MALDI-TOF MS (LD+): m/z (%) = 745.2
(100) [M + 23]+
˙
, 723.2 (25) [M]+
˙
, 340.5 (33). IR (film):
734, 912, 1149, 1194, 1248, 1374, 1451, 1518, 1649, 1658, 1730, 2848,
2873, 2923, 2957, 3354 cm-¹.