References and Notes
<A NAME="RG34406ST-1">1</A>
Current Address: CARBOGEN AMCIS AG, 5502 Hunzenschwil, Switzerland.
<A NAME="RG34406ST-2">2</A>
The term ‘mycolactone’ usually refers to the naturally occurring mixture of mycolactones
A and B, which are geometric isomers at the C4′=C5′ double bond. Although both isomers
can be isolated separately, each of them rapidly isomerizes to the mixture of mycolactones
A and B.
<A NAME="RG34406ST-3">3</A>
George KM.
Chatterjee D.
Gunawardana G.
Welty D.
Hayman J.
Lee R.
Small PL.
Science
1999,
283:
854
<A NAME="RG34406ST-4">4</A>
Adusumilli S.
Mve-Obiang A.
Sparer T.
Meyers W.
Hayman J.
Small PL.
Cell. Microbiol.
2005,
7:
1295
<A NAME="RG34406ST-5">5</A>
Coutanceau E.
Marsollier L.
Brosch R.
Perret E.
Goossens P.
Tanguy M.
Cole ST.
Small PL.
Demangel C.
Cell. Microbiol.
2005,
7:
1187
<A NAME="RG34406ST-6">6</A>
George KM.
Pascopella L.
Welty DM.
Small PL.
Infect. Immun.
2000,
68:
877
<A NAME="RG34406ST-7">7</A>
Benowitz AB.
Fidanze S.
Small PL.
Kishi Y.
J. Am. Chem. Soc.
2001,
123:
5128
<A NAME="RG34406ST-8">8</A>
Song F.
Fidanze S.
Benowitz AB.
Kishi Y.
Org. Lett.
2002,
4:
647
<A NAME="RG34406ST-9A">9a</A> The synthesis and structure confirmation of mycolactone C, which is a ca. 1:1
mixture of 12′-deoxymycolactones A and B is described in:
Judd TC.
Bischoff A.
Kishi Y.
Adusumilli S.
Small PLC.
Org. Lett.
2004,
6:
4901
<A NAME="RG34406ST-9B">9b</A> Mycolactone C is the major metabolite of Australian strains of M. ulcerans and it is 10,000-fold less cytopathic than mycolactones A and B:
Mve-Obiang A.
Lee RE.
Portaels F.
Small PLC.
Infect. Immun.
2003,
71:
774
<A NAME="RG34406ST-9C">9c</A>
West African strains of M. ulcerans produce mycolactone C only as a minor metabolite.
<A NAME="RG34406ST-10">10</A>
Gurjar MK.
Cherian J.
Heterocycles
2001,
55:
1095
<A NAME="RG34406ST-11">11</A>
Van Summeren RP.
Feringa BL.
Minnaard AJ.
Org. Biomol. Chem.
2005,
3:
2524
<A NAME="RG34406ST-12">12</A>
Yin N.
Wang G.
Qian M.
Negishi E.
Angew. Chem. Int. Ed.
2006,
45:
2916 ; Angew. Chem. 2006, 118, 2982
<A NAME="RG34406ST-13">13</A> Leadlay and co-workers have recently reported the isolation and structure elucidation
of new mycolactones from a pathogenic strain of M. ulcerans from China (MU98912). In comparison with mycolactones A and B from the African strain
MUAgy99, these new mycolactones incorporate an additional methyl group attached to
C2′. MU98912 does not produce mycolactones A/B:
Hong H.
Spencer JB.
Porter JL.
Leadlay PF.
Stinear T.
ChemBioChem
2005,
6:
643
<A NAME="RG34406ST-14">14</A>
Alexander MD.
Fontaine SD.
La Clair JJ.
DiPasquale AG.
Rheingold AL.
Burkart MD.
Chem. Commun.
2006,
4602
For recent reviews on olefin metathesis cf., e.g.:
<A NAME="RG34406ST-15A">15a</A>
Grubbs RH.
Tetrahedron
2004,
60:
7117
<A NAME="RG34406ST-15B">15b</A>
Trnka TM.
Grubbs RH.
Acc. Chem. Res.
2001,
34:
18
<A NAME="RG34406ST-16A">16a</A>
Oppolzer W.
Blagg J.
Rodriguez I.
Walther E.
J. Am. Chem. Soc.
1990,
112:
2767
<A NAME="RG34406ST-16B">16b</A>
Nguyen G.
Perlmutter P.
Rose ML.
Vounatsos F.
Org. Lett.
2004,
6:
893
<A NAME="RG34406ST-17A">17a</A>
Carreira EM.
Du Bois J.
J. Am. Chem. Soc.
1995,
117:
8106
<A NAME="RG34406ST-17B">17b</A> See also:
Eis MJ.
Wrobel JE.
Ganem B.
J. Am. Chem. Soc.
1984,
106:
3693
<A NAME="RG34406ST-18">18</A>
Wang Y.
Dong X.
Larock RC.
J. Org. Chem.
2003,
68:
3090
<A NAME="RG34406ST-19">19</A>
Dess DB.
Martin JC.
J. Am. Chem. Soc.
1991,
113:
7277
<A NAME="RG34406ST-20">20</A>
Kraus GA.
Roth B.
J. Org. Chem.
1980,
45:
4825
<A NAME="RG34406ST-21">21</A>
White JD.
Blakemore PR.
Green NJ.
Hauser EB.
Holoboski MA.
Keown LE.
Nylund Kolz CS.
Phillips BW.
J. Org. Chem.
2002,
67:
7750
<A NAME="RG34406ST-22">22</A>
Aïssa C.
Riveiros R.
Ragot J.
Fürstner A.
J. Am. Chem. Soc.
2003,
125:
15512
<A NAME="RG34406ST-23">23</A>
The reaction of 14a with (+)-Ipc2B(CH2CH=CH2) represents the mismatched reactant combination. The matched case [reaction of ent-14a with (+)-Ipc2B(CH2CH=CH2)] has been reported by Fürstner and co-workers to produce the syn product in good yield and with excellent selectivity (see ref. 22).
<A NAME="RG34406ST-24">24</A>
Höfle G.
Steglich W.
Vorbrüggen H.
Angew. Chem. Int. Ed. Engl.
1978,
17:
569 ; Angew. Chem. 1978, 90, 602
<A NAME="RG34406ST-25">25</A>
Preparation of 16: To a solution of diene 3 (565 mg, 0.97 mmol) in CH2Cl2 (320 mL, 0.003 M) was added [1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]
dichloro(phenylmethylene)(tricyclohexylphosphine)Ru (Grubbs’ II catalyst; 42 mg, 0.075
mmol) and the mixture was heated to reflux for 4 h (with additional 21 mg of catalyst
being added after 2 h). After cooling to r.t., H2O (50 mL) was added to the reaction mixture and a part of the solvent was removed
under reduced pressure. The layers were separated and the aqueous solution was extracted
with CH2Cl2 (2 × 30 mL). The combined organic extracts were dried over MgSO4 and the solvent was evaporated in vacuo. Purification of the residue by flash chromatography
in EtOAc-hexane (1:10) gave 16 (391 mg, 72%) as a faintly yellow, viscous oil; [α]20
D -44.0° (c = 0.61, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.3 Hz, 2 H), 7.35 (d, J = 8.0 Hz, 2 H), 4.85-4.97 (m, 2 H), 4.02-4.08 (m, 1 H), 3.80-3.86 (m, 1 H), 3.37-3.42
(m, 1 H), 2.46 (s, 3 H), 2.35-2.43 (m, 2 H), 2.00-2.11 (m, 2 H), 1.58-1.94 (m, 6 H),
1.65 (s, 3 H), 1.30-1.45 (m, 2 H), 0.90-0.99 (m, 15 H), 0.60 (q, J = 8.0 Hz, 6 H). 13C NMR (100 MHz, CDCl3): δ = 173.2, 144.8, 138.1, 132.9, 129.8, 128.0, 120.4, 77.6, 72.5, 71.6, 45.3, 37.6,
35.6, 33.5, 33.3, 31.4, 21.7, 21.6, 18.7, 15.7, 13.4, 7.0, 5.1. IR (film): 2954, 2912,
2876, 1731, 1366, 1244, 1176, 1022, 969, 815, 672 cm-
1. HRMS (ESI, +ve): m/z [M + Na]+ calcd for C29H48O6SSi: 575.2833; found: 575.2827.
The assignment of the newly formed double bond as E was based on the absence of cross peaks between the C8-methyl group and C9-H in both
NOESY and ROSY experiments. As expected for an E configured double bond between C8 and C9 a strong NOE cross peak was observed between
C9-H and the 7-CH2 moiety.
<A NAME="RG34406ST-26">26</A>
Zhou J.
Fu GC.
J. Am. Chem. Soc.
2003,
125:
12527
<A NAME="RG34406ST-27">27</A>
Encouraged by the efficiency and selectivity of ring closure observed with RCM substrate
3, we have also investigated triene 17 as a possible substrate for RCM-mediated formation of the 12-membered ring (Figure
[3]
). However, treatment of this compound with Grubbs’ second-generation catalyst did
not produce any of the desired 12-membered macrolactone. Instead, and perhaps not
too surprisingly, the major product formed in the reaction appears to be cyclohexene
18 (based on MS analysis of the reaction mixture).