Total synthesis of (.+-.)-wikstromol

Belletire, J. L.; Fry, D. F.

doi:10.1021/jo00255a012

Cited by 57 publications

(18 citation statements)

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“…Partial acetylation (one equivalent of Ac 2 O and excess pyridine in CH 2 Cl 2 ) of the diol in a known alkaloid, deacetyllycoclavine (15), afforded the same product as that obtained by reduction of 13 above, demonstrating the stereochemistry of the hydroxyl group at C-5 in 16 to be b-orientation. The thus-obtained C-6 monoacetylated compound (16) was subjected to esterification with O-benzyl 3-(4-hydroxy-3-methoxylphenyl)propanoic acid (18), 40) which was prepared from commercially available ferulic acid. Finally, the protecting group on the phenol group was removed by hydrogenolysis to furnish the target compound, which was found to be completely identical with natural 10 by comparison of their chromatographic behavior and spectroscopic data including [a] D .…”

Section: Ten New Lycopodium Alkaloidsmentioning

confidence: 99%

Ten New Lycopodium Alkaloids Having the Lycopodane Skeleton Isolated from Lycopodium serratum THUNB.

Takayama

Katakawa

Kitajima

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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(10), having lycopodine-related structures, were isolated from the club moss Lycopodium serratum THUNB. and their structures were elucidated on the basis of spectroscopic analysis and/or chemical transformation.Key words alkaloid; Lycopodium; structure elucidation; X-ray crystal structure; NMR; chemical transformation Lycoposerramine-G (2) was obtained as a colorless amorphous powder. HR-FAB-MS analysis gave m/z 280.1893 (MϩH) ϩ (D Ϫ2.0 mmu) and established the molecular formula as C 16 H 25 NO 3 , which was one oxygen atom less than 1 described above. The 1 H-and 13 C-NMR (Table 1) spectra of 2, which resembled those of 1 except for the chemical shifts of the carbons adjacent to nitrogen, indicated that 1 was an N-oxide derivative of 2. Actually, when 2 was treated with one equivalent of m-CPBA, lycoposerramine-F (1) was obtained in 63% yield, thereby establishing the structure of the new alkaloid as formula 2.Lycoposerramine-H (3) was obtained as colorless prisms (mp 227-228°C, sublimation). HR-FAB-MS analysis gave m/z 262.1809 (MϩH) ϩ (D ϩ0.2 mmu) and established the molecular formula as C 16 H 23 NO 2 , which indicated that 3 had one extra unsaturated number compared to common lycopodine-type alkaloids.1 H-and 13 C-NMR spectra (see Table 1) as well as DEPT spectra suggested the presence of one ketone, a trisubstituted olefin bearing a methyl group, one sp 3 quaternary carbon, four sp 3 methines (one of which had a hydroxyl function), and seven sp 3 methylenes. 1 H-1 H COSY and HMQC spectra revealed connectivities as shown by the bold line in Fig. 3. Further, allyl couplings between the olefinic proton (d 5.35, H-8) and methyl protons (d 1.58, H-16) and methylene protons (d 1.98, 2.70, H-14), as well as homoallyl coupling between the methyl protons (H-16) and the methine proton (d 2.52, H-7), indicated the presence of a double bond at the C-8 (d 121.6)-C-15 (d 135.9) position of the lycopodine skeleton. The location of the secondary hydroxyl group was inferred from the HMBC cross-peaks between the proton at d 3.78 (d, Jϭ2.7 Hz) and the carbonyl carbon (d 212.4, C-5) and the methine carbon at d 38.7 (C-4). The structure including the stereochemistry of the secondary hydroxyl group at C-6 was determined by X-ray analysis as formula 3 (Fig. 3). This is the first example of a lycopodine-type alkaloid that has a double bond at the C-8-C-15 position.Lycoposerramine-I (4) showed a molecular ion peak at m/z 261 and the molecular formula, C 16 H 23 NO 2 , which was established by HR-FAB-MS [m/z 262.1802 (MϩH) ϩ , D Ϫ0.5 mmu], was identical with that of 3 described above. Comparison of its1 H-and 13 C-NMR spectra (see Table 1) with those of 3 suggested that the two alkaloids were isomers at the position of the secondary hydroxyl group. The chemical shifts at C-10 (d 35.5), C-11 (d 69.2), and C-12 (d 44.6) in 4 as well as the HMBC cross-peak (Fig. 4) between the low-field proton (d 4.34) and the quaternary carbon at C-13 (d 59.7) indicated that the hydroxyl group existed at the C-11 position. The stereochemistry...

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Section: Ten New Lycopodium Alkaloidsmentioning

confidence: 99%

Ten New Lycopodium Alkaloids Having the Lycopodane Skeleton Isolated from Lycopodium serratum THUNB.

Takayama

Katakawa

Kitajima

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Enterolactone 13] (10), a dibenzylbutane lignan produced in the human gut via bacterial fermentation of fiber and implicated in the prophylactic action of high fiber diets against colon cancer (11), was prepared in 50% overall yield by a seven-step dianion coupling sequence (12) beginning with a commercially available cinnamic acid. Wikstromol {4] (13), a lignan possessing significant antitumor activity, has been synthesized (14) in racemic form by a similar ninestep dianion coupling sequence proceeding in 29% overall yield from commercially available starting material. Hinokinin [5] (15) is readily made (6) in 60% overall yield from 3,4-(methylenedioxy)hydrocinnamic acid in a sequence also involving, as its key step, dianion coupling.…”

Section: Resultsmentioning

confidence: 99%

The Role of Dianion Coupling in the Synthesis of Dibenzylbutane Lignans

Belletire

Fry²,

Fremont³

1992

J. Nat. Prod.

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Dianion coupling reactions have been used to prepare structurally related lignan natural products in racemic form. A readily available alpha-idocarboxylic acid 10 has been employed in separate sequences to afford the tetrahydrofuran lignan burseran [6] and the butyrolactone lignan deoxypodorhizon [7]. The key strategy for both burseran and deoxypodorhizon involved reaction of the appropriate dianion with an alpha-iodo carboxylate salt 13. Equilibration under acid or base was employed to create the trans stereochemistry of the substituted benzyl side chains of both burseran and deoxypodorhizon. To achieve proper dianion reactivity and to avoid side reactions in the synthetic sequence to deoxypodorhizon, it was necessary to develop the chemistry of acylsulfonamide dianions. As a further structure proof, our synthetic deoxypodorhizon was also utilized as a substrate in a successful sequence to isostegane [8], a known relay intermediate to the antineoplastic prototype steganacin [9].

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“…Thus, the alkylphenol 7, which is the potential alarm pheromone of the marine mollusk Haminoea callidegenita, was synthesized using the acid 1f (R = 4-OH). 12 The antineoplastic prototype lignan natural product wikstromol (8) 13 and also natural phenol dihydrocurcumin (9) 14 were prepared based on the acid 1g (R = 4-OH-3-OMe). The acid 1h (R = 4-NO 2 ) is suitable not only as a protective group, but also an effective stereo-differentiating group in the synthesis of desoxycholic acid analogue 10.…”

Section: Application Of Hydrocinnamic Acidsmentioning

confidence: 99%

“…In contrast, Grignard reagents and organozinc derivatives obtained from the corresponding 2-phenylethyl halides 41a-c are sufficiently effective to produce hydrocinnamic acids 1 when reacted with CO 2 (RMgCl: 1a, 87%; 57a RMgBr: 43, 62%; 57b RZnI: 1a, 60% 57c ). This approach was, in particular, used in the synthesis of 13 Alternative possibilities to convert phenylethyl halides 41a-c into hydrocinnamic acid (1a) include their condensation with KCN (92%) 57e or Me 3 SiCN (97%) 57f to produce the corresponding nitrile intermediates, which give excellent yields of the target acid on hydrolysis.…”

Section: Scheme 12mentioning

confidence: 99%

Hydrocinnamic Acids: Application and Strategy of Synthesis

Korneev¹

2013

Synthesis

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This review summarizes all the main approaches to the synthesis of hydrocinnamic acids based on the construction of the side chain with a carboxy moiety around the aromatic ring. Numerous methods for the synthesis of hydrocinnamic acids by constructive or destructive routes, such as reductive or oxidative reactions, rearrangements, catalytic reactions, or electrochemical conversion, are considered and presented in a rational system.

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Total synthesis of (.+-.)-wikstromol

Cited by 57 publications

References 0 publications

Ten New Lycopodium Alkaloids Having the Lycopodane Skeleton Isolated from Lycopodium serratum THUNB.

Ten New Lycopodium Alkaloids Having the Lycopodane Skeleton Isolated from Lycopodium serratum THUNB.

The Role of Dianion Coupling in the Synthesis of Dibenzylbutane Lignans

Hydrocinnamic Acids: Application and Strategy of Synthesis

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