A convenient synthesis of the central core of helioporins, seco-pseudopterosins and pseudopterosins in racemic form is reported, using a Suzuki coupling (A-ring formation)-Friedel-Crafts acylation sequence, followed by synthetic elaboration of the resulting tetralone derivative. Key steps of the method are a totally diastereoselective cuprate conjugate addition and a final, spontaneous Friedel-Crafts acylation.
TanakaJ, OgawaN, LiangJ, HigaT, GrávalosDG. (1993) Heliporins: bioactive diterpenes from the blue coral Helipora coerulea. Tetrahedron, 49, 811–822.
2.
LookSA, FenicalW, JacobsRS, ClardyJ. (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;
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LookSA, FenicalW, MatsumotoGK, ClardyJ. (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;
4.
LookSA, FenicalW. (1987) The seco-pseodopteosins, new anti-inflammaytory diterpene-glycosides from a Caribbean gorgonian octocoral of the genus Pseudopterogorgia. Tetrahedron, 43, 3363–3370;
5.
HaroisCA, BurchMT, FenicalW. (1988) New marine diterpenoids, including a unique hydroperoxide, from a Caribbean gorgonian coral of the genus Pseudopterogorgia. Tetrahedron Letters, 29, 4361–4364;
6.
RoussisV, WuZ, FenicalW, StrobelSA, Van DuyneGD, ClardyJ. (1990) New anti-inflammatory pseudopterosins from the marine octocoral Pseudopterogorgia elisa bethae. Journal of Organic Chemistry, 55, 4916–4922;
7.
AtaA, KerrRG, MoyaCE, JacobsRS. (2003) Identification of anti-inflammatory diterpenes from the marine gorgonian Pseudopterogorgia elisabethae. Tetrahedron, 59, 4215–4222;
8.
AtaA, WinHY, HoltD, HollowayP, SegstroEP, JayatilakeGS. (2004) New antibacterial diterpenes from Pseudopterogorgia elisabethae. Helvetia Chimica Acta, 87, 1090–1098;
9.
RodriguezII, ShingYP, GarciaOJ, RodriguezAD, MayerMS, SánchezJA, Ortega-BarriaE, GonzálezJ. (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;
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DuqueC, PuyanaM, NarváezG, OsornoO, HaraN, FujimotoY. (2004) Pseudopterosins P–V, new compounds from the gorgonian octocoral Pseudopterogorgia elisabethae from Providencia island, Colombian Caribbean. Tetrahedron, 60, 10627–10635;
11.
DuqueC, PuyanaM, CastellanosL, AriasA, CorreaH, OsornoO, AsaiT, HaraN, FujimotoY. (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.
12.
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.
13.
The benzodioxole unit of helioporins is a functionality relatively rare in marine natural products. See: (a) HigaT. (1991) in Bioorganic Marine Chemistry, ScheuerPJ. (Ed.). Springer-Verlag, Berlin, Vol. 4, pp 33–90;
14.
VenkateswarluY, FaulknerDJ, SteinerJLR, CorcoranE, ClardyJ. (1991) Smenochromenes, unusual macrocyclic sesquiterpene hydroquinone derivatives from a Seychelles sponge of the genus Smenospongia. Journal of Organic Chemistry, 56, 6271–6274.
15.
Revision of the proposed structure: LazerwithSE, JohnsonTW, CoreyEJ. (2000) Syntheses and stereochemical revision of pseudopterosin G-J aglycon and helioporin E. Organic Letters, 2, 2389–2392.
16.
DehmelF, SchmalzHG (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.
17.
HorstermanD, SchmalzHG, Kociok-KohnG (1999) Synthesis of an analog of the cytotoxic marine diterpene helioporin C exploiting arene-Cr(CO)3 chemistry. Tetrahedron, 55, 6905–6916.
18.
GellerT, SchmalzHG, BatsJW. (1998) Chiral arene-Cr(CO)3 complexes in organic synthesis: A short enantioselective total synthesis of putative helioporin D. Tetrahedron Letters, 39, 1537–1540;
19.
GellerT, JakupovicJ, SchmalzHG. (1998) Preparation of helioporin D from the seco-pseudopterosin aglycone: Revision of the stereostructure of helioporin D. Tetrahedron Letters, 39, 1541–1544.
20.
Preliminary account: Benoit-MarquieF, CsakyAG, EstebanG, MartínezME, PlumetJ. (2000) An expeditious entry to the hydrophenalene ring system of pseudopterosins. Tetrahedron Letters, 41, 3555–3558.
21.
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: BrokaCA, ChanS, PetersonB. (1988) Total synthesis of (-)-pseudopterosin A. Journal of Organic Chemistry, 53, 1584–1586;
22.
from (1S,2R,5S)-(-)-menthol: CoreyEJ, CarpinoP. (1989) Enantiospecific total synthesis of pseudopterosins A and E. Journal of the American Chemical Society, 111, 5472–5474;
23.
from (S)-(-)-citronellal: CoreyEJ, CarpinoP. (1990) A new enantiospecific route to the pseudopterosins. Tetrahedron Letters, 31, 3857–3858;
24.
from aryl-substituted 1-tetralones: GangulyAK, McCombieSW, CoxB, LinSI, McPhailAT. (1990) Stereospecific synthesis of the aglycone of pseudopterosin E. Pure and Applied Chemistry, 62, 1289–1291;
25.
McCombieSW, CoxB, GangulyAK. (1991) Controlling benzylic functionality and stereochemistry: 2. Synthesis of the pseudopterosin aglycone. Tetrahedron Letters, 32, 2087–2090;
26.
SchmalzHG, SchwarzA, DürnerG. (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;
27.
SchmalzHG, SiegelS, SchwarzA. (1996) Radical cyclization of η6-arene-Cr(CO)3 complexes: A regio- and stereoselective entry to functionalized pseudopterosin precursors. Tetrahedron Letters, 37, 2947–2950;
28.
MajdalamiA, SchamalzHG. (1997) Enantioselective synthesis of the aglycones of pseudopterosin and seco-pseudopterosin via a common synthetic intermediate. Synlett, 1303–1305;
29.
from (S)-(+)-carvone: KozikovskiAP, WuJP. (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;
30.
from 3-ethoxy-5-methylcyclohexanone: JungME, SiedemCS. (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
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JungME, LeeBS. (2000) Unusual α-methylation of alkoxyaryl ketones with higher order methyl cuprate and lithium bromide. Journal of Organic Chemistry, 65, 9241–9244;
32.
EcklundL, SarvaryI, FrejdT. (1996) Synthetic studies towards pseudopterosin A. Journal of the Chemical Society. Perkin Transactions I, 303–305;
33.
from (1R, 2S, 5R)- (-)-isopulegol: GillS, KocienskiP, KohlerA, PontiroliA, QunL. (1996) A synthetic approach to the pseudopterosins. Journal of the Chemical Society. Chemical Communications, 1743–1744. See also:
34.
ChowR, KocienskiP, KuhlA, LeBrazidecJY, MuirK, FishP. (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;
35.
KocienskiP, PontiroliA, QunL. (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.
36.
from γ-methylen-γ-butirolactone: HarrowvenDC, DennisonST, HolmesP. (1994) A synthetic approach to the pseudopterosins using cascade technology. Tetrahedron Letters, 35, 4243–4246;
37.
HarrowvenDC, WildenJD, TyteMJ, HursthouseMB, ColesSJ. (2001) A new approach to the pseudopterosins using an arene alkylation with a γ-methylene-γ-butyrolactone. Tetrahedron Letters, 42, 1193–1195. see also:
38.
HarrowvenDC, SibleyGEM. (1999) The sequential annulation of an arene with a tetrahydrofuran provides a new route to the pseudopterosins. Tetrahedron Letters, 40, 8299–8300;
39.
HarrowvenDC, TyteMJ. (2004) Total synthesis of (±)-pseudopterosin A–F and K–L aglycone. Tetrahedron Letters, 45, 2089–2091;
40.
from anilides via oxidation to o-imidoquinones using Dess-Martin periodinane: NicolauKC, ZhongYL, BaranPS, SugitaK. (2001) Rapid access to complex molecular architectures via o-azaquinones. Angewandte Chemie International Edition, 40, 2145–2149. See also:
41.
NicolauKC, SugitaK, BaranPS, ZhongYL. (2002) Iodine (V) reagents in organic synthesis. Part 2. Access to complex molecular architectures via Dess-Martin periodinane-generated o-imidoquinones. Journal of the American Chemical Society, 124, 2221–2232.
42.
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) SchmalzHG, MajdalamiA, GellerT, HollanderJ, BatsJW. (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;
43.
MajdalamiA, SchamalzHG. (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.
44.
CowinLM, Massy-WestroppRA. (1992) Selective reduction of serrulatenol as a route to seco pseudopterosin analogues. Journal of Natural Products, 55, 1790–1794.
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EstebanG, López-SánchezMA, MartínezME, PlumetJ. (1998) A convenient procedure for the synthesis of 1-tetralone derivatives using a Suzuki coupling-Friedel-Crafts acylation sequence. Tetrahedron, 54, 197–212.
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49.
The behaviour of compounds 10 and 15 towards the metallation reaction using nBuLi was very different. In the case of compound 15 the sequence o-metallation-capture with TMSCl allowed for the synthesis of 2,3-dimethoxy-4-(trimethylsilyl)-toluene (69–73% isolated yield depending on the reaction conditions). In the case of compound 10 only 17 was obtained under a variety of experimental conditions.
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For a general treatise see: (a) SuzukiA.; BrownH.C. in Organic Synthesis via Boranes. Vol 3: “Suzuki coupling”. Aldrich Chemical Co., 2003.
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SuzukiA. (1991) Synthetic studies via the cross-coupling reaction of organoboron derivatives with organic halides. Pure and Applied Chemistry, 63, 419–422;
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56.
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Ch-eT, MiyauraN, SuzukiA. (1993) Palladium-catalyzed cross-coupling reaction of organoboron compounds with organic triflates. Journal of Organic Chemistry, 58, 2201–2208;
58.
FürstnerA, SeidelG. (1998) Suzuki reactions with B-allyl-9-borabicyclo[3.3.1]nonane (B-allyl-9-BBN). Synlett, 161–162;
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BrownHC, ChenJC. (1981) Hydroboration. 57. Hydroboration with 9-borabicyclo[3.3.1]nonane of alkenes containing representative functional groups. Journal of Organic Chemistry, 46, 3978–3988.
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64.
Polyphosphate ester was prepared from P2O5 and CHCl3 in Et2O. See: (a) Rama-RaoAV, ChandaB, BorateHB. (1982) A convenient approach to the total synthesis of (±) 4-demethoxydaunomycinone. Tetrahedron, 38, 3555–3561;
65.
Rama-RaoAV, YadavJS, ReddyKK, UpenderV (1991) Total syntheses of (±) cervinomycins A1 and A2. Tetrahedron Letters, 32, 5199–5202.
66.
CoreyEJ, ChaikowskyM. (1965) Dimethyloxosulfonium methylide ((CH3)2SOCH2) and dimethylsulfonium methylide ((CH3)2SCH2). Formation and application to organic synthesis. Journal of the American Chemical Society, 87, 1353–1364.
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Lower overall yields were obtained when the reaction was carried out in the absence of TMSCl. See: (a) ChuitC, FoulonJP, NormanJF. (1980) Action des dialkylcuprates de lithium sur les aldéhydes α,β– éthylénioues. Tetrahedron, 36, 2305–2310;
69.
ChuitC, FoulonJP, NormanJF. (1981) Réactivité des dérivés organocuivreux vis-à-vis des aldéhydes αβ-éthyléniques. Tetrahedron, 37, 1385–1389. See also:
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AlexakisA, BerlanJ, BesaceY. (1986) Organocopper conjugate addition reaction in the presence of trimethylchlorosilane. Tetrahedron Letters, 27, 1047–1050.
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CroftKD, GhisalbertiEL, JefferiesPR, ProufootGM. (1981) The chemistry of Eremophila spp. XVI. New serrulatanes from Eremophila spp. Australian Journal of Chemistry, 34, 1951–1957.
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