A Short and Efficient TotalSynthesis of the Naturally Occurring Coumarins Siderin, Kotanin,Isokotanin A and Desertorin C

Abstract

Starting from methyl 2-hydroxy-4-methoxy-6-methylbenzoate (6) and its regioisomeric dehydrodimers 7-9,readily available by an oxidative coupling reaction of 6, the naturally occurring coumarins siderin(1), kotanin (2),isokotanin A (3) and desertorin C (4) were synthesized in a novel and highlyefficient three-step transformation. In the case of kotanin (2) both atropisomers were prepared fromthe pure atropisomers of 7.

atropisomerism - biaryls - oxidative phenoliccoupling - natural coumarins

References

<A NAME="RT05603SS-1">1</A> Bringmann G. Günther C. Ochse M. Schupp O. Tasler S. Prog.Chem. Org. Nat. Prod.  2001,  82:  1 

<A NAME="RT05603SS-2">2</A> Stothers JB. Stoessl A. Can. J. Chem.  1988,  66:  2816 

<A NAME="RT05603SS-3A">3a</A> Büchi G. Luk KC. Kobbe B. Townsend JM. J. Org.Chem.  1977,  42:  244 

<A NAME="RT05603SS-3B">3b</A>

See also Refs. [2] [4b] [7a]

<A NAME="RT05603SS-4A">4a</A> Laakso JA. Narske ED. Gloer JB. Wicklow DT. Dowd PF. J.Nat. Prod.  1994,  57:  128 

<A NAME="RT05603SS-4B">4b</A> Nozawa K. Nakajima S. Kawai K.-I. Udagawa SI. Miyaji M. Phytochemistry  1994,  35:  1049 

<A NAME="RT05603SS-5">5</A> Nozawa K. Seyea H. Nakajima S. Udagawa SI. Kawai KI. J. Chem. Soc., Perkin Trans. 1  1987,  1735 

Siderin(1):

<A NAME="RT05603SS-6A">6a</A> Venturella P. Bellino A. Piozzi F. TetrahedronLett.  1974,  15:  979 

<A NAME="RT05603SS-6B">6b</A> Chexal KK. Fouweather C. Holker JSE. J. Chem. Soc., Perkin Trans. 1  1974,  554 

<A NAME="RT05603SS-6C">6c</A> Ahluwalia VK. Kumar D. Indian J. Chem.,Sect. B  1976,  14:  589 

Kotanin(2)

<A NAME="RT05603SS-7A">7a</A> Racemic: Büchi G. Klaubert DH. Shank RC. Weinreb SM. Wogan GN. J.Org. Chem.  1971,  36:  1143 

<A NAME="RT05603SS-7B">7b</A> Stereoselective: Lin G.-Q. Zhong M. Tetrahedron:Asymmetry  1997,  8:  1369 

Isokotanin A(3)

<A NAME="RT05603SS-8A">8a</A> Racemic: Lin G.-Q. Zhong M. Acta Chim.Sin.  1997,  55:  97 ; Chem. Abstr. 1997, 126, 211942

<A NAME="RT05603SS-8B">8b</A> Stereoselective: Lin G.-Q. Zhong M. TetrahedronLett.  1996,  37:  3015 

<A NAME="RT05603SS-8C">8c</A> Stereoselective: Bringmann G. Hinrichs J. Henschel P. Kraus J. Peters K. Peters E.-M. Eur.J. Org. Chem.  2002,  1096 

Desertorin C(4)

<A NAME="RT05603SS-9A">9a</A> Racemic: Rizzacasa MA. Sargent MV. J. Chem. Soc., PerkinTrans. 1  1988,  2425 

<A NAME="RT05603SS-9B">9b</A> Stereoselective: Kyasnoor RV. Sargent MV. Chem. Commun.  1998,  2713 

<A NAME="RT05603SS-9C">9c</A> Steroselective: Baker RW. Kyasnoor RV. Sargent MV. Skelton BW. White AH. Aust.J. Chem.  2000,  53:  487 

<A NAME="RT05603SS-10">10</A>

The total syntheses of the three biarylcoumarins 2-4 require ca.25 steps according to the literature.

<A NAME="RT05603SS-11A">11a</A> Drochner D. Hüttel W. Nieger M. Müller M. Angew. Chem.Int. Ed.  2003,  42:  931 ; Angew. Chem. 2003, 115, 961

<A NAME="RT05603SS-11B">11b</A>

Drochner, D.; Karl,U.; Nieger, M., Müller, M.; Steglich, W., manuscript inpreparation.

<A NAME="RT05603SS-12">12</A> Similar reactions are reported inthe literature. However, yields are low and reaction conditionscannot be applied to substrate 6., e.g.: Connor DT. Sorenson RJ. J. Heterocycl. Chem.  1981,  18:  587 

<A NAME="RT05603SS-13">13</A> Long RS. J.Am. Chem. Soc.  1947,  69:  990 

<A NAME="RT05603SS-14">14</A> Basi ski W. Polish J. Chem.  1995,  69:  376 ; Chem. Abstr. 1995, 123, 32908

<A NAME="RT05603SS-15">15</A> Szabó V. Borda J. Theisz E. ActaChim. Acad. Sci. Hung.  1980,  103:  271 ; Chem. Abstr. 1981, 94, 103116

<A NAME="RT05603SS-16A">16a</A> Suzuki E. Katsuragawa B. Inoue S. Synthesis  1978,  144 

<A NAME="RT05603SS-16B">16b</A> See also Refs.

<A NAME="RT05603SS-17">17</A>

This was demonstrated for the 6,8′-bisaminochromenone 15, which was converted to desertorin C(4) in a single step. Hence, the hydrolyticmixture was dehydrated chemically with dimethyl carbonate afterno starting material could be detected (TLC). Acetyl chloride wasadded to generate additional HCl. The yield (34%) is comparableto the overall yield of the two-step procedure (36%).

<A NAME="RT05603SS-18">18</A>

The low yield in the case of M-(-)-2 ismainly due to a nonoptimized reaction time for acidic hydrolysis.

<A NAME="RT05603SS-19">19</A>

The isomers of kotanin(2)were erroneously mismatched in a previous publication. [11a]

<A NAME="RT05603SS-20A">20a</A> Chiarello J. Joullié MM. Tetrahedron  1988,  44:  41 

<A NAME="RT05603SS-20B">20b</A> Sala T. Sargent MV. J. Chem. Soc., Perkin Trans.Trans.1  1981,  855 

<A NAME="RT05603SS-21">21</A>

Crystallographic data (excluding structurefactors) for the structures reported in this paper have been depositedwith the Cambridge Crystallographic Data Centre as supplementary publicationno. CCDC-215646. Copies of the data can be obtained free of chargeat www.ccdc.cam.ac.uk/conts/retrieving.html [orfrom the Cambridge Crystallographic Data Centre, 12 Union Road,Cambridge CB2 1EZ, UK; Fax: int. code+44-1223/336-033;e-mail: [e-mail]].