A Convenient Synthesis of the Central Core of Helioporins,seco -Pseudopterosins and Pseudopterosins via BCA-Annulation Sequence

Tanaka J , Ogawa N , Liang J , Higa T , Grávalos DG . (1993) Heliporins: bioactive diterpenes from the blue coral Helipora coerulea. Tetrahedron, 49, 811–822.

[2] (a) Look SA , Fenical W , Jacobs RS , Clardy J. (1986) The pseudopterosins: anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae. Proceedings of the National Academy of Sciences of the United States of America, 83, 6238–6240;

(b) Look SA , Fenical W , Matsumoto GK , Clardy J. (1986) The pseudopterosins: A new class of anti-inflammatory and analgesic diterpene pentosides from the marine sea whip Pseudopterogorgia elisabethae (Octocorallia). Journal of Organic Chemistry, 51, 5140–5145;

(c) Look SA , Fenical W. (1987) The seco-pseodopteosins, new anti-inflammaytory diterpene-glycosides from a Caribbean gorgonian octocoral of the genus Pseudopterogorgia. Tetrahedron, 43, 3363–3370;

(d) Harois CA , Burch MT , Fenical W. (1988) New marine diterpenoids, including a unique hydroperoxide, from a Caribbean gorgonian coral of the genus Pseudopterogorgia. Tetrahedron Letters, 29, 4361–4364;

(e) Roussis V , Wu Z , Fenical W , Strobel SA , Van Duyne GD , Clardy J. (1990) New anti-inflammatory pseudopterosins from the marine octocoral Pseudopterogorgia elisa bethae. Journal of Organic Chemistry, 55, 4916–4922;

(f) Ata A , Kerr RG , Moya CE , Jacobs RS . (2003) Identification of anti-inflammatory diterpenes from the marine gorgonian Pseudopterogorgia elisabethae. Tetrahedron, 59, 4215–4222;

(g) Ata A , Win HY , Holt D , Holloway P , Segstro EP , Jayatilake GS . (2004) New antibacterial diterpenes from Pseudopterogorgia elisabethae. Helvetia Chimica Acta, 87, 1090–1098;

(h) Rodriguez II , Shing YP , Garcia OJ , Rodriguez AD , Mayer MS , Sánchez JA , Ortega-Barria E , González J. (2004) New pseudopterosin and seco-pseudopterosin diterpene glycosides from two Colombian isolates of Pseudopterogorgia elisabethae and their diverse biological activities. Journal of Natural Products, 67, 1672–1680;

(i) Duque C , Puyana M , Narváez G , Osorno O , Hara N , Fujimoto Y. (2004) Pseudopterosins P–V, new compounds from the gorgonian octocoral Pseudopterogorgia elisabethae from Providencia island, Colombian Caribbean. Tetrahedron, 60, 10627–10635;

(j) Duque C , Puyana M , Castellanos L , Arias A , Correa H , Osorno O , Asai T , Hara N , Fujimoto Y. (2006) Further studies on the constituents of the gorgonian octocoral Pseudopterogorgia elisabethae collected in San Andrés and Providencia islands, Colombian Caribbean: isolation of a putative biosynthetic intermediate leading to erogorgiaene. Tetrahedron, 62, 4205–4213.

In the original paper of Higa et al., the stereochemical relationship between the methyl groups at positions 7 and 3 (compounds 2 and 3) and 4 and 11 (compounds 5–9) were described as trans (7β-methyl in 2 and 3 and 4β-methyl in 5–9). These stereochemical arrangements have been corrected though unequivocal total synthesis of compounds 3 and 5–7. The corrected structures are represented in Figure 1 for these compounds. See references 5–8.

The benzodioxole unit of helioporins is a functionality relatively rare in marine natural products. See: (a) Higa T. (1991) in Bioorganic Marine Chemistry, Scheuer PJ . (Ed.). Springer-Verlag, Berlin, Vol. 4, pp 33–90;

(b) Venkateswarlu Y , Faulkner DJ , Steiner JLR , Corcoran E , Clardy J. (1991) Smenochromenes, unusual macrocyclic sesquiterpene hydroquinone derivatives from a Seychelles sponge of the genus Smenospongia. Journal of Organic Chemistry, 56, 6271–6274.

Revision of the proposed structure: Lazerwith SE , Johnson TW , Corey EJ . (2000) Syntheses and stereochemical revision of pseudopterosin G-J aglycon and helioporin E. Organic Letters, 2, 2389–2392.

Dehmel F , Schmalz HG (2001) Unexpected endo selectivity of conjugate nucleophilic addition to an arene-Cr(CO)₃ complex: enantioselective synthesis of the diterpene 11-epi-helioporin B. Organic Letters, 3, 3579–3582.

Horsterman D , Schmalz HG , Kociok-Kohn G (1999) Synthesis of an analog of the cytotoxic marine diterpene helioporin C exploiting arene-Cr(CO)₃ chemistry. Tetrahedron, 55, 6905–6916.

[8] (a) Geller T , Schmalz HG , Bats JW . (1998) Chiral arene-Cr(CO)₃ complexes in organic synthesis: A short enantioselective total synthesis of putative helioporin D. Tetrahedron Letters, 39, 1537–1540;

(b) Geller T , Jakupovic J , Schmalz HG . (1998) Preparation of helioporin D from the seco-pseudopterosin aglycone: Revision of the stereostructure of helioporin D. Tetrahedron Letters, 39, 1541–1544.

Preliminary account: Benoit-Marquie F , Csaky AG , Esteban G , Martínez ME , Plumet J. (2000) An expeditious entry to the hydrophenalene ring system of pseudopterosins. Tetrahedron Letters, 41, 3555–3558.

For previous synthesis of the hexahydro-1H-phenalene ring system of helioporins A and E and pseudopterosins, see reference 5 and: (a) from (S)-(-)-limonene: Broka CA , Chan S , Peterson B. (1988) Total synthesis of (-)-pseudopterosin A. Journal of Organic Chemistry, 53, 1584–1586;

(b) from (1S,2R,5S)-(-)-menthol: Corey EJ , Carpino P. (1989) Enantiospecific total synthesis of pseudopterosins A and E. Journal of the American Chemical Society, 111, 5472–5474;

(c) from (S)-(-)-citronellal: Corey EJ , Carpino P. (1990) A new enantiospecific route to the pseudopterosins. Tetrahedron Letters, 31, 3857–3858;

(d) from aryl-substituted 1-tetralones: Ganguly AK , McCombie SW , Cox B , Lin SI , McPhail AT . (1990) Stereospecific synthesis of the aglycone of pseudopterosin E. Pure and Applied Chemistry, 62, 1289–1291;

(e) McCombie SW , Cox B , Ganguly AK . (1991) Controlling benzylic functionality and stereochemistry: 2. Synthesis of the pseudopterosin aglycone. Tetrahedron Letters, 32, 2087–2090;

(f) Schmalz HG , Schwarz A , Dürner G. (1994) Chiral η⁶-arene-Cr(CO)₃ complexes as synthetic building blocks: An enantio- and diastereoselective approach to substituted hydrophenalenes related to helioporin E and pseudopterosin G. Tetrahedron Letters, 35, 6861–6864;

(g) Schmalz HG , Siegel S , Schwarz A. (1996) Radical cyclization of η⁶-arene-Cr(CO)₃ complexes: A regio- and stereoselective entry to functionalized pseudopterosin precursors. Tetrahedron Letters, 37, 2947–2950;

(h) Majdalami A , Schamalz HG . (1997) Enantioselective synthesis of the aglycones of pseudopterosin and seco-pseudopterosin via a common synthetic intermediate. Synlett, 1303–1305;

(i) from (S)-(+)-carvone: Kozikovski AP , Wu JP . (1991) A general approach to the pseudopterosins and their C-11 and C-13 stereoisomers. Construction of the tricyclic skeleton of the pseudopterosins. Synlett, 465–468;

(j) from 3-ethoxy-5-methylcyclohexanone: Jung ME , Siedem CS . (1993) Efficient synthesis of a hexasubstituted aromatic ring via an intramolecular Michael-aldol process: preparation of a late tricyclic intermediate for the synthesis of pseudopterosin A. Journal of the American Chemical Society, 115, 3822–3823. See also

(k) Jung ME , Lee BS . (2000) Unusual α-methylation of alkoxyaryl ketones with higher order methyl cuprate and lithium bromide. Journal of Organic Chemistry, 65, 9241–9244;

(l) Ecklund L , Sarvary I , Frejd T. (1996) Synthetic studies towards pseudopterosin A. Journal of the Chemical Society. Perkin Transactions I, 303–305;

(m) from (1R, 2S, 5R)- (-)-isopulegol: Gill S , Kocienski P , Kohler A , Pontiroli A , Qun L. (1996) A synthetic approach to the pseudopterosins. Journal of the Chemical Society. Chemical Communications, 1743–1744. See also:

(n) Chow R , Kocienski P , Kuhl A , LeBrazidec JY , Muir K , Fish P. (2001) Enantiospecific syntheses of pseudopterosin aglycones. Part 1. Synthesis of the putative aglycone of pseudopterosin G–J via an A->AB-> ABC annulation strategy. Journal of the Chemical Society. Perkin Transactions I, 2344–2355;

(o) Kocienski P , Pontiroli A , Qun L. (2001) Enantiospecific syntheses of pseudopterosin aglycones. Part 2. Synthesis of the putative aglycone of pseudopterosin G–J via an A->AB-> ABC annulation strategy. Journal of the Chemical Society. Perkin Transactions I, 2356–2366.

(p) from γ-methylen-γ-butirolactone: Harrowven DC , Dennison ST , Holmes P. (1994) A synthetic approach to the pseudopterosins using cascade technology. Tetrahedron Letters, 35, 4243–4246;

(q) Harrowven DC , Wilden JD , Tyte MJ , Hursthouse MB , Coles SJ . (2001) A new approach to the pseudopterosins using an arene alkylation with a γ-methylene-γ-butyrolactone. Tetrahedron Letters, 42, 1193–1195. see also:

(r) Harrowven DC , Sibley GEM . (1999) The sequential annulation of an arene with a tetrahydrofuran provides a new route to the pseudopterosins. Tetrahedron Letters, 40, 8299–8300;

(s) Harrowven DC , Tyte MJ . (2004) Total synthesis of (±)-pseudopterosin A–F and K–L aglycone. Tetrahedron Letters, 45, 2089–2091;

(t) from anilides via oxidation to o-imidoquinones using Dess-Martin periodinane: Nicolau KC , Zhong YL , Baran PS , Sugita K. (2001) Rapid access to complex molecular architectures via o-azaquinones. Angewandte Chemie International Edition, 40, 2145–2149. See also:

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For previous synthesis of the tetrahydronaphto[1,2-d]ring system and of the related helioporins and seco-pseudopterosins aglycon, see references 6–8 and: (a) Schmalz HG , Majdalami A , Geller T , Hollander J , Bats JW . (1995) Diastereoselective transformation of chiral η⁶-Arene-Cr(CO)₃ complexes: Enantioselective synthesis of functionalized hydronaphthalene derivatives related to the seco-pseudopterosins. Tetrahedron Letters, 36, 4777–4780;

(b) Majdalami A , Schamalz HG . (1997) Chiral η⁶-arene-Cr(CO)₃ complexes in organic synthesis: A short and highly selective synthesis of the 18-nor-seco-pseudopterosin aglycone. Tetrahedron Letters, 38, 4545–4548.

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