Subscribe to RSS
DOI: 10.1055/s-0031-1290339
Total Synthesis and Stereochemical Revision of Burkholdac A
Publication History
Publication Date:
08 February 2012 (online)
![](https://www.thieme-connect.de/media/synlett/201205/lookinside/thumbnails/10.1055-s-0031-1290339-1.jpg)
Abstract
A stereocontrolled total synthesis of burkholdac A was completed, leading to a revision of the reported stereochemistry.
Key words
burkholdac A - total synthesis - antitumor - stereochemical assignment
- Supporting Information for this article is available online:
- Supporting Information
- 1
Montaser R.Hendrik L. Future Med. Chem. 2011, 3: 1475 - 2
Suyama TL.Gerwick WH.McPhail KL. Bioorg. Med. Chem. 2011, 19: 6675 - 3
Maier ME. Nat. Prod. Rep. 2009, 26: 1105 -
4a
Wang L.Xu ZS.Ye T. Org. Lett. 2011, 13: 2506 -
4b
Liu H.Liu Y.Xu ZS.Ye T. Chem. Commun. 2010, 46: 7486 -
4c
Li S.Chen Z.Xu ZS.Ye T. Chem. Commun. 2010, 46: 4773 -
4d
Gao XG.Liu Y.Kwong S.Xu ZS.Ye T. Org. Lett. 2010, 12: 3018 -
4e
Chen Z.Song L.Xu ZS.Ye T. Org. Lett. 2010, 12: 2036 -
4f
Jin Y.Liu YQ.Wang Z.Kwong S.Xu ZS.Ye T. Org. Lett. 2010, 12: 1100 -
4g
Liang S.Xu ZS.Ye T. Chem. Commun. 2010, 46: 153 -
4h
Chen B.Dai L.Zhang H.Tan W.Xu ZS.Ye T. Chem. Commun. 2010, 46: 574 -
4i
Li S.Liang S.Tan WF.Xu ZS.Ye T. Tetrahedron 2009, 65: 2695 -
4j
Li S.Liang S.Xu ZS.Ye T. Synlett 2008, 569 -
4k
Ren Q.Dai L.Zhang H.Tan W.Xu ZS.Ye T. Synlett 2008, 2379 -
4l
Chen Z.Ye T. New J. Chem. 2006, 30: 518 -
4m
Pang HW.Xu ZS.Chen ZY.Ye T. Lett. Org. Chem. 2005, 2: 699 -
4n
Peng YG.Pang HW.Xu ZS.Ye T. Lett. Org. Chem. 2005, 2: 703 -
4o
Peng YG.Pang HW.Ye T. Org. Lett. 2004, 6: 3781 -
4p
Xu ZS.Chen ZY.Ye T. Tetrahedron: Asymmetry 2004, 15: 355 -
4q
Xu ZS.Peng YG.Ye T. Org. Lett. 2003, 5: 2821 -
4r
Chen ZY.Deng JG.Ye T. ARKIVOC 2003, (vii): 268 - 5
Benelkebir H.Donlevy AM.Packham G.Ganesan A. Org. Lett. 2011, 13: 6334 - 6
Biggins JB.Gleber CD.Brady SF. Org. Lett. 2011, 13: 1536 -
7a
Chen Y.Gambs C.Abe Y.Wentworth P.Janda KD. J. Org. Chem. 2003, 68: 8902 -
7b
Cheng YQ.Yang M.Matter AM. Appl. Environ. Microbiol. 2007, 73: 3460 -
7c
Narita K.Kikuchi T.Watanabe K.Takizawa T.Oguchi T.Kudo K.Matsuhara K.Abe H.Yamori T.Yoshida M.Katoh T. Chemistry 2009, 15: 11174 -
7d
Wang C.Wesener SR.Zhang H.Cheng YQ. Chem. Biol. 2009, 16: 585 - 8
Brooks DW.Lu LDL.Masamune S. Angew. Chem., Int. Ed. Engl. 1979, 18: 72 - 9
Yurek-George A.Habens F.Brimmell M.Packham G.Ganesan A. J. Am. Chem. Soc. 2004, 130: 1026 - 10
Keck GE.Boden EP. J. Org. Chem. 1985, 50: 2394 -
11a
Nagao Y.Hagiwara Y.Kumagai T.Ochiai M.Inoue T.Hashimoto K.Fujita E. J. Org. Chem. 1986, 51: 2391 -
11b
White JD.Martin WHC.Lincoln C.Yang J. Org. Lett. 2007, 9: 3481 -
11c
Janssen D.Kalesse M. Synlett 2007, 2667 -
11d
Scheerer JR.Lawrence JF.Wang GC.Evans DA. J. Am. Chem. Soc. 2007, 129: 8968 -
11e
Smith AB.Simov V. Org. Lett. 2006, 8: 3315 -
11f
Paterson I.Steven A.Luckhurst CA. Org. Biomol. Chem. 2004, 2: 3026 -
11g
Romo D.Choi NS.Li S.Buchler I.Shi Z.Liu JO. J. Am. Chem. Soc. 2004, 126: 10582 -
11h
Velazquez F.Olivo HF. Curr. Org. Chem. 2002, 6: 303 -
11i
Sinz CJ.Rychnovsky SD. Angew. Chem. Int. Ed. 2001, 40: 3224 -
11j
Aiguadé J.González A.Urpí F.Vilarrasa J. Tetrahedron Lett. 1996, 37: 8949 -
12a
Shiina I.Kubota M.Oshiumi H.Hashizume M. J. Org. Chem. 2004, 69: 1822 -
12b
Shiina I.Fukui S.Sasaki A. Nat. Protoc. 2007, 2: 2312
References and Notes
Synthesis of the
Proposed Burkholdac A (1)
Compound 2 (46
mg, 0.04 mmol) was dissolved in MeOH-CH2Cl2 (50
mL, 1:9) and added to a vigorously stirred solution of I2 (126
mg, 0.50 mmol) in MeOH-CH2Cl2 (200 mL,
1:9) at r.t. over 0.5 h. After 10 min, the reaction was quenched
by addition of sat. aq solution of Na2S2O3 (20
mL) and concentrated in vacuo. The residue was extracted with EtOAc
(3 × 30 mL). The combined organic layers were washed with
sat. aq solution of Na2S2O3 (20
mL) and brine (30 mL), dried over anhyd Na2SO4 and
concentrated in vacuo. The residue was dissolved in pyridine (1
mL), after HF˙py (0.8 mL) was added at 0 ˚C,
the reaction mixture was stirred at r.t. for 12 h. All volatiles
were removed in vacuo; the residue was diluted with EtOAc (100 mL)
and washed with HCl (20 mL, 1.0 M in H2O) and brine (20
mL), dried over anhyd Na2SO4 and concentrated
in vacuo. The residue was purified by flash chromatography (eluted
with EtOAc-hexanes-MeOH = 3:1:0.3)
to provide the desired compound 1 (13.4
mg, 63% yield over 2 steps) as a white amorphous solid: [α]D
²0 -166.5
(c 0.35, MeOH). ¹H
NMR (400 MHz, CD3CN): δ = 7.71 (d, J = 5.4 Hz,
1 H), 7.09 (d, J = 9.8
Hz, 1 H), 7.02 (br s, 1 H), 5.90 (br s, 1 H), 5.77 (d, J = 15.5 Hz,
1 H), 5.58 (dd, J = 6.1,
2.3 Hz, 1 H), 4.74 (br s, 1 H), 3.97-3.92 (m, 1 H), 3.83
(ddd, J = 10.2,
6.5, 4.0 Hz, 1 H), 3.68 (td, J = 10.3,
3.0 Hz, 1 H), 3.40-3.22 (m, 2 H), 2.73-2.67 (m,
2 H), 2.64-2.56 (m, 3 H), 2.51-2.43 (m, 3 H),
2.40-2.26 (m, 3 H), 2.18-2.08 (m, 2 H), 2.06 (s,
3 H), 0.83 (d, J = 0.8
Hz, 3 H), 0.81 (d, J = 1.0
Hz, 3 H) ppm. ¹³C NMR (100 MHz, CD3CN): δ = 172.4,
171.4, 171.2, 170.8, 131.9, 131.0, 70.0, 69.6, 60.1, 54.9, 54.8,
43.7, 41.2, 41.2, 41.1, 31.4, 29.1, 28.3, 20.8, 15.6, 15.0 ppm.
ESI-HRMS m/z calcd for C22H36N3O6S3
+ [M + H]+:
534.1761; found: 534.1757.
The Analytical
Data of the Revised Burkholdac A (
epi-
1)
[α]D
²0 -54.0
(c 0.23, MeOH). ¹H
NMR (500 MHz, CD3CN): δ = 7.51 (s,
1 H), 7.41 (d, J = 6.9
Hz, 1 H), 6.90 (d, J = 8.9 Hz,
1 H), 6.12-6.06 (m, 1 H), 5.90 (d, J = 15.5
Hz, 1 H), 5.56-5.54 (m, 1 H), 4.70 (td, J = 9.2,
3.6 Hz, 1 H), 4.47-4.43 (m, 1 H), 4.18-4.13 (m,
1 H), 3.33-3.30 (m, 1 H), 3.21 (d, J = 10.5
Hz, 1 H), 3.13 (d, J = 14.0
Hz, 1 H), 2.96 (dd, J = 13.1,
7.2 Hz, 1 H), 2.86-2.57 (m, 8 H), 2.25 (dq, J = 13.6,
6.8 Hz, 1 H), 2.10 (s, 3 H), 2.08-2.01 (m, 2 H), 0.96 (d, J = 6.8 Hz,
3 H), 0.87 (d, J = 6.8
Hz, 3 H) ppm. ¹³C NMR (125 MHz, CD3CN): δ = 173.0,
172.2, 171.7, 170.1, 132.4, 131.5, 71.7, 69.0, 63.2, 56.8, 56.4,
41.8, 41.1, 40.8, 33.3, 31.2, 30.6, 30.5, 21.1, 19.8, 15.2 ppm.
ESI-HRMS: m/z calcd for C22H36N3O6S3
+ [M + H]+:
534.1761; found: 534.1760.