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DOI: 10.1055/s-0029-1217976
Stereoselective Formal Total Synthesis of (-)-Didemniserinolipid B
Publication History
Publication Date:
10 September 2009 (online)
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Abstract
A formal total synthesis of (-)-didemniserinolipid B from l-(+)-tartaric acid is presented. Key features of the synthesis include construction of the bicyclic acetal core from bisdimethyl amide of tartaric acid and further elaboration by cross metathesis.
Key words
didemniserinolipid B - marine natural product - stereoselective synthesis - tartaric acid
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Ref. 5 and 6
References and Notes
Formation of minor amount (8%) of diketone resulting from the addition of Grignard reagent to both amide groups is observed.
8Diastereomeric ratio of the product alcohol was estimated to be >95:5 within detectable limits by ¹H NMR. Alcohols were inseparable at this stage. However, stereochemistry of the alcohol is of no consequence because it is deoxygenated in the next step.
11It was cumbersome to purify the cross-metathesis product 12 by column chromatography from traces of an unidentified impurity. However, this was of no consequence in the next reaction sequence, and pure 13 was isolated after the reduction of the olefin and the ester.
12All new compounds exhibited satisfactory
spectral data. In the NMR data that follow, * indicates
rotamer peaks.
Compound 3: [α]D +8.7
(c 1.3, CHCl3). IR (neat):
2940, 2863, 1716, 1652, 1506, 1374 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.40-7.24
(m, 5 H), 5.13 (d, J = 6.0
Hz, 1 H), 4.78 (d, J = 5.7
Hz, 1 H), 4.90 (s, 2 H), 3.47 (t, J = 6.0
Hz, 2 H), 3.13 (s, 3 H), 2.98 (s, 3 H), 2.83-2.56 (m, 2
H), 1.79-1.55 (m, 4 H), 1.42 (s, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 209.2, 168.1,
138.5, 128.3, 128.3, 127.6, 127.5, 112.1, 82.1, 74.9, 72.9, 69.9,
39.2, 37.0, 36.0, 29.1, 26.4, 26.0, 19.8. HRMS: m/z calcd
for C18H25NO5 + Na: 386.1943;
found: 386.1925
Compound 13: [α]D -21.2
(c 3, CHCl3). IR (neat): 3448, 2926,
1455, 1097, 734 cm-¹. ¹H
NMR (300 MHz, CDCl3):
δ = 7.50-7.10
(m, 10 H), 4.62 (s, 2 H), 4.5 (s, 2 H), 4.17 (br s, 1 H), 3.90-3.73
(m, 1 H), 3.63 (t, J = 6.6
Hz, 2 H), 3.46 (t, J = 6.6
Hz, 2 H), 3.29 (br s, 1 H), 2.30 (t, J = 7.5
Hz, 2 H), 2.00-1.15 (m, 40 H). ¹³C
NMR (75 MHz, CDCl3): δ = 138.7, 138.5,
128.37, 128.32, 127.63, 127.58, 127.47, 109.3, 80.0, 77.8, 72.8,
72.3, 70.3 (2 C), 63.1, 37.4, 35.3, 32.8, 30.7, 29.8, 29.62, 29.58,
29.41, 26.1, 25.7, 25.4, 22.8, 22.0. HRMS:
m/z calcd for C40H62O5 + Na:
645.4495; found: 645.4484.
Compound 15: [α]D -18.3
(c 0.3, CHCl3). IR (neat):
3069, 2927, 1700, 1454, 1388, 734 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.50-7.20
(m, 10 H), 4.61 (s, 2 H), 4.49 (s, 2 H), 4.17 (br s, 1 H), 4.10-3.85
(m, 3 H), 3.85-3.70 (m, 1 H), 3.70-3.30 (m, 6
H), 3.29 (br s, 1 H), 2.00-1.15 (m, 55 H).
¹³C
NMR (100 MHz, CDCl3): δ = 152.2/151.7*,
138.7/138.5*, 128.4, 128.35, 127.66, 127.60, 127.5,
109.3, 93.7/93.3*, 80.1/79.7*,
80.0, 77.8, 72.9, 72.3, 71.4, 70.3 (2 C), 70.1/69.3*,
65.7/65.4*, 56.5/56.4*, 37.43,
35.3, 30.8, 29.8, 29.7, 29.64, 29.60, 29.5, 28.48, 28.43, 27.5/26.8*,
26.11, 26.06, 25.43, 24.4/23.1*, 22.8, 21.96.
HRMS: m/z calcd for C51H81NO8 + Na:
858.5860; found: 858.5861.
Compound 16: [α]D -41.4
(c 1.2, CHCl3) [Lit.4d [α]D +36.3 (c 0.2, CHCl3 for the enantiomer)].
IR (CHCl3): 3463, 2928, 1700, 1389, 1366, 1088, 770 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 4.07 (br
s, 1 H), 4.05-3.96 (m, 1 H), 3.95-3.86 (m, 3 H),
3.65 (t, J = 6.5
Hz, 2 H), 3.62-3.55 (m, 1 H), 3.54-3.37 (m, 2
H), 3.36-3.14 (m, 2 H), 2.52-2.30 (m, 1 H), 2.10-1.81
(m, 1 H), 1.79-1.41 (m, 30 H), 1.38-1.22 (m, 25
H).
¹³C NMR (100 MHz, CDCl3): δ = 152.2/151.7*,
109.6, 93.7/93.3*, 82.4, 80.3/79.7*,
77.8, 71.4, 70.0/69.3*, 66.3, 65.7/65.4*,
56.5/56.3*, 37.5, 35.2, 32.7, 30.2, 29.8, 29.7
(2 C), 29.6 (2 C), 29.5, 28.48/28.43*, 27.5/26.8*,
26.1, 25.6, 25.3, 25.1, 24.4/23.1*, 23.0. HRMS: m/z calcd for C37H69NO8 + Na:
678.4921; found: 678.4935.
Compound 18: [α]D -29.3
(c 0.3, CHCl3) [Lit.4b [α]D +37.6 (c 0.98, CHCl3)]. ¹H
NMR (400 MHz, CDCl3): δ = 6.95 (dt, J = 15.5,
7.0 Hz, 1 H), 5.80 (d, J = 15.6
Hz, 1 H), 4.17 (q, J = 7.2
Hz, 2 H), 4.06 (br s, 1 H), 4.02-3.96 (m, 1 H), 3.95-3.81
(m, 3 H), 3.61 (br s, 1 H), 3.59-3.24 (m, 4 H), 2.50-2.26 (m,
1 H), 2.19 (q, J = 7.0
Hz, 2 H), 2.16-1.36 (m, 25 H), 1.35-1.21 (m, 33
H). ¹³C NMR (100 MHz, CDCl3): δ = 166.7,
152.5/151.7*, 148.8, 121.4, 109.6, 93.7/93.2*,
82.3, 80.3/79.7*, 77.6, 71.3, 69.97/69.19*,
66.2, 65.6/65.3*, 60.1, 56.4/56.3*,
37.4, 35.0, 32.0, 30.0, 29.7, 29.4, 28.7/28.4*, 27.8,
27.4/26.7*, 26.0, 25.0, 24.3/23.0*,
22.9, 14.2. HRMS: m/z calcd
for C41H73NO9 + Na: 746.5183;
found: 746.5188.