References
1a
Pilli RA.
Ferreira de Olivera MC.
Nat. Prod. Rep.
2000,
17:
117
1b
Lin W.-H.
Ye Y.
Xu R.-S.
J. Nat. Prod.
1992,
55:
571
2a
Qin GW.
Xu RS.
Med. Res. Rev.
1998,
18:
375
2b
Ye Y.
Qin G.-W.
Xu R.-S.
Phytochemistry
1994,
37:
1201
2c
Ye Y.
Qin G.-W.
Xu R.-S.
Phytochemistry
1994,
37:
1205
2d
Ye Y.
Qin G.-W.
Xu R.-S.
J. Nat. Prod.
1994,
57:
655
2e
Brem B.
Seger C.
Pacher P.
Hofer O.
Vajrodaya S.
Greger H.
J. Agric. Food Chem.
2002,
50:
6383
3a Tuberostemonine: Wipf P.
Rector SR.
Takahashi H.
J. Am. Chem. Soc.
2002,
124:
14848
3b For stenine see the following: Morimoto Y.
Iwahashi M.
Nishida K.
Hayashi Y.
Shirahama H.
Angew. Chem., Int. Ed. Engl.
1996,
35:
904
3c
Morimoto Y.
Iwahashi M.
Kinoshita T.
Nishida K.
Chem.-Eur. J.
2001,
7:
4107
3d
Wipf P.
Kim Y.
Goldstein DM.
J. Am. Chem. Soc.
1995,
117:
11106
3e
Golden JE.
Aube J.
Angew. Chem. Int. Ed.
2002,
41:
4316
3f
Chen CY.
Hart DJ.
J. Org. Chem.
1993,
58:
3840
3g
Ginn JD.
Padwa A.
Org. Lett.
2002,
4:
1515
For other stemona alkaloids see the following:
3h Williams DR.
Fromhold MG.
Earley JD.
Org. Lett.
2001,
3:
2721
3i
Kende AS.
Martin Hernando JI.
Milbank JBJ.
Tetrahedron
2002,
58:
61
3j
Martin SF.
Barr KJ.
Smith DW.
Bur SK.
J. Am. Chem. Soc.
1999,
121:
6990
Enantioselective synthesis:
4a
Gurjar MK.
Reddy DS.
Tetrahedron Lett.
2002,
43:
295
4b
Jacobi PA.
Lee K.
J. Am. Chem. Soc.
2000,
122:
4295
4c
Kinoshita A.
Mori M.
Heterocycles
1997,
46:
287
4d
Kinoshita A.
Mori M.
J. Org. Chem.
1996,
61:
8356
4e
Williams DR.
Reddy JP.
Amato GS.
Tetrahedron Lett.
1994,
35:
6417
For racemic synthesis see the following:
4f
Jacobi PA.
Lee K.
J. Am. Chem. Soc.
1997,
119:
3409
4g
Kohno Y.
Narasaka K.
Bull. Chem. Soc. Jpn.
1996,
69:
2063
5 Ester 10 is commercially available.
6
Acevedo CM.
Kogut EF.
Lipton MA.
Tetrahedron
2001,
57:
6353 . The alcohol is also commercially available
7a Ref. 6.
7b
Frieman BA.
Bock CW.
Bhat KL.
Heterocycles
2001,
55:
2099
8 For an example of alkylation of protected pyroglutamyl alcohol see: Sato Y.
Saito N.
Mori M.
Tetrahedron
1998,
54:
1153 ; also see refs. 4b, 4d
For stereoselective olefination of prolinal derivatives see:
9a
Langois N.
Radom M.-O.
Tetrahedron Lett.
1998,
39:
857
9b
Mulzer J.
Shanyoor M.
Tetrahedron Lett.
1993,
34:
6545
9c
Moriwake T.
Hamano S.
Miki D.
Saito S.
Torii S.
Chem. Lett.
1986,
815
9d
Clark JS.
Hodgson PB.
Goldsmith MD.
Blake AJ.
Cooke PA.
Street LJ.
J. Chem. Soc., Perkin Trans. 1
2001,
3325
9e
Lee E.
Li KS.
Lim J.
Tetrahedron Lett.
1996,
37:
1445
For conjugate addition to γ-amino alkenoates with varied levels of syn selectivity see:
10a
Moriwake T.
Hamano S.
Saito S.
Heterocycles
1988,
27:
1135
10b
Le Coz S.
Mann A.
Thareau F.
Taddei M.
Heterocycles
1993,
36:
2073
10c
Reetz MT.
Röhrig D.
Angew. Chem., Int. Ed. Engl.
1989,
28:
1706
10d
Jako I.
Uiber P.
Mann A.
Taddei M.
Wermuth CG.
Tetrahedron Lett.
1990,
31:
1011
10e
Jako I.
Uiber P.
Mann A.
Wermuth CG.
Boulanger T.
Norberg B.
Evrard G.
Durant F.
J. Org. Chem.
1991,
56:
5729
10f
Hanessian S.
Sumi K.
Synthesis
1991,
1083
10g
Hanessian S.
Demont E.
van Otterlo WAL.
Tetrahedron Lett.
2000,
41:
4999
10i
Hanessian S.
Wang W.
Gai Y.
Tetrahedron Lett.
1996,
37:
7477
10j
Paz MM.
Sardina FJ.
J. Org. Chem.
1993,
58:
6990
For examples of highly diastereoselective conjugate additions of copper reagents to γ-substituted alkenoates and discussions on stereoselectivity in these reactions see:
11a
Yamamoto Y.
Chounan Y.
Nishii S.
Ibuka T.
Kitahara H.
J. Am. Chem. Soc.
1992,
114:
7652
11b
Roush WR.
Lesur BM.
Tetrahedron Lett.
1983,
24:
2231
11c
Roush WR.
Michaelides MR.
Tai DF.
Lesur BM.
Chong WKM.
Harris DJ.
J. Am. Chem. Soc.
1989,
111:
2984
12
Procedure for Conjugate Addition: Lithium bromide (2.59 g, 30.1 mmol, 6 equiv) and CuBr·DMS (3.059 g, 15.0 mmol) were placed in a dry round bottomed flask. THF (35 mL) was added to the solids and the reaction mixture was cooled to -78 °C. Vinyl magnesium bromide (30 mL, 0.977 molar solution in THF, 6 equiv) was added dropwise. After stirring for 30 min at the same temperature, ester 8 (1.1072 g, 5 mmol) in THF (10 mL) was added dropwise and the resultant solution was stirred at the same temperature for 10 min and at -40 °C for 50 min. The reaction was quenched with NH4Cl solution and extracted with Et2O repeatedly. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography using EtOAc and hexane (EtOAc-hexane, 1:1) to give the ester 7 (1.02 g, 81%). 1H NMR (500 MHz, CDCl3): δ = 1.69-1.76 (m, 1 H), 1.95-2.04 (m, 1 H), 2.25-2.39 (m, 4 H), 2.29 (d, J = 7.0 Hz, 2 H), 2.93 (m, 1 H), 3.05-3.11 (m, 1 H), 3.66 (s, 3 H), 3.75-3.84 (m, 2 H), 5.04 (d, J = 10.0 Hz, 1 H), 5.08 (d, J = 17.5 Hz, 1 H), 5.18 (dd, J = 13.5, 3 Hz, 2 H), 5.73 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 19.5, 30.4, 31.7, 32.4, 39.9, 41.3, 52.1, 60.0, 117.3, 117.9, 135.3, 136.7, 172.7, 175.6. IR (neat): 1733, 1674 cm-1. [α]D
25 +17.3 (c = 1.0, MeOH). HRMS: m/z calcd for C14H21NO3Na+: 274.1413; found: 274.1410. The stereochemistry at C-9 was unambiguously established at a later stage (compounds 15 and 17).
13 Interestingly, conjugate addition to the corresponding Z-ester gave a 2:1 mixture of diastereomers with 7 as the major product (data not shown).
14a For recent reviews on ring-closing metathesis see: Trnka TM.
Grubbs RH.
Acc. Chem. Res.
2001,
34:
18
14b Also see: Fürstner A.
Angew. Chem. Int. Ed.
2000,
39:
3012
For the formation of 7-membered azacycles using RCM see the following:
14c
Turling CA.
Holmes AB.
Markwell RE.
Pearson ND.
J. Chem. Soc., Perkin Trans. 1
1999,
1695
14d
Barrett AGM.
Ahmed M.
Baker SP.
Baugh SPD.
Braddock DC.
Procopiou PA.
White AJP.
Williams DJ.
J. Org. Chem.
2000,
65:
3716
14e
Martin SF.
Chen H.-J.
Courtney AK.
Liao Y.
Pätzel M.
Ramser MN.
Wagman AS.
Tetrahedron
1996,
52:
7251
14f
Colombo L.
Di Giacomo M.
Vinci V.
Colombo M.
Manzoni L.
Scolastico C.
Tetrahedron
2003,
59:
4501
14g
Vo-Thanh G.
Boucard V.
Sauriat-Dorizon H.
Guibe F.
Synlett
2001,
37
14h
Lim SH.
Ma S.
Beak P.
J. Org. Chem.
2001,
66:
9056
14i
Beal LM.
Liu B.
Chu W.
Moeller KD.
Tetrahedron
2000,
56:
10113
14j
Hoffmann T.
Lanig H.
Waibel R.
Gmeiner P.
Angew. Chem. Int. Ed.
2001,
40:
3361
14k
Grossmith CE.
Senia F.
Wagner J.
Synlett
1999,
1660
15
Preparation of the Tricyclic Lactam 6: The iodolactone 17 (0.748 g, 2.2 mmol) was dissolved in degassed toluene (75 mL) in a two-neck round-bottomed flask fitted with a reflux condenser and a rubber septum. Tributyltin hydride (0.722 mL, 2.68 mmol) was added and the reaction heated to 80 °C. A solution of AIBN (60 mg) in toluene (5 mL) was added to the reaction mixture four times with the interval of 1 h. The resultant solution was refluxed for 10 h. The solvent was removed and the residue was chromatographed over silica gel to give 6 as a highly viscous liquid that solidified upon cooling (0.321 g, 70%); mp 42-43 °C. 1H NMR (500 MHz, CDCl3): δ = 1.51-1.60 (m, 2 H), 1.70 (q, J = 10.5 Hz, 1 H), 1.83-1.85 (m, 1 H), 2.02-2.08 (m, 1 H), 2.36-2.41 (m, 4 H), 2.47-2.53 (m, 1 H), 2.60-2.70 (m, 1 H), 2.76-2.87 (m, 1 H), 4.0 (dt, J = 6.0, 10.5 Hz, 1 H), 4.11-4.14 (m, 1 H), 4.27 (dt, J = 3.0, 10.5 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 22.9, 25.7, 30.8, 31.2, 34.8, 40.4, 45.1, 56.3, 80.0, 174.3, 174.9. [α]D
25 -91.9 (c = 1.0, CHCl3). HRMS: m/z calcd for C11H15NO3Na: 232.0944; found: 232.0940.
16 Also see ref. 4c for a similar reduction and establishment of stereocenter at C-9 and C-10.
17 Lactone 6 could also be methylated to provide C-9, C-10 diepi stemoamide (data not shown).
18 Mp: 185-186 °C. 1H NMR (500 MHz, CDCl3): δ = 1.31 (d, J = 6.9 Hz, 3 H), 1.50-1.58 (m, 2 H), 1.72 (quint, J = 10.7 Hz, 1 H), 1.85-1.90 (m, 1 H), 2.0-2.10 (m, 1 H), 2.38-2.45 (m, 4 H), 2.60 (dq, J = 6.9, 12.5 Hz, 1 H), 2.65 (dd, J = 12.3, 14.1 Hz, 1 H), 3.99 (dt, J = 10.8, 6.3 Hz, 1 H), 4.16 (m, 1 H), 4.20 (dt, J = 3.1, 10.3 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 14.1, 22.5, 25.6, 30.5, 34.8, 37.3, 40.2, 52.7, 55.8, 77.6, 174.0, 177.3. IR (neat): 1768, 1681 cm-1. [α]D
25 -191.6 (c = 0.5, MeOH). {Lit. [α]D
25 -183.5 (c = 1.36, MeOH);
[4b]
[α]D
30 -219.3 (c = 0.5, MeOH);
[4d]
[α]D -181.6
(c = 0.89, MeOH)}.
[4e]
HRMS: m/z calcd for C12H17NO3Na+: 246.1100: found: 246.1099.