Approaches to the Synthesis of Aromatic Diterpenes Oxygenated in the A Ring. Synthesis of Margocin

Burnell, Robert H.; Côté, Christian; Théberge, Nathalie

doi:10.1021/np50099a004

Cited by 12 publications

(4 citation statements)

References 18 publications

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“…H20 was added, and cc (petroleum ether/4096 Et20) of the product obtained by Et20 extraction gave alcohol 3 (148 mg, 9496): *H nmr 2.23 (s, 3-Me), 3.82 (s, MeO), 4.53 (s, 2H, CH2OH), 6.78 (d,7=8.9 Hz, H-5), 7.11 (s, H-2), 7.13 (d,7=8.9 Hz, H-6); eims mlz [ 152 (100), 137 (90), 121 (25), 109 (24), 108 (31), 107 (17), 91 (52), 77 (35). 4-Metboxy-3-methylbenzyl bromide [4).-To a solution of 3 (2.09 g) in C6H6 (300 ml) at 0°was added pyridine (1.22 ml) and then PBr3 (0.9 ml). After 4 h stirring, the mixture was poured into HzO/dilute HC1, Et20 extracted, and the residue chromatographed (petroleum ether/596 Et20) to give 4 (2.87 g, 9796): nmr 2.23 (s, 3-Me), 3.83 (s, MeO), 4.50 (s, 2H, CH2Br), 6.78 (d,7=9.1 Hz, H-5), 7.19 (s, H-2), 7.21 (d, 7=9.1 Hz,: eims mlz 216, [M]+ 214 (3), 135 (100), 91 (24).…”

Section: Methodsmentioning

confidence: 99%

“…For the next step no separation was required, and oxidative decyanation at this position afforded 12 identical with methyl nimbiol (1) as judged by the comparison of spectral data. 0-Methyl nimbinone [14} was also synthesized in optically active form from methyl 0-methyl podocarpate [16} derived from natural podocarpic acid following the methodology used previously to corroborate the structure of margocin (4). The key intermediate was the allylic alcohol 27, which was prepared as follows.…”

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confidence: 99%

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Synthesis of O-Methyl Nimbinone

Burnell¹,

Dumont²,

Théberge³

1993

J. Nat. Prod.

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Two syntheses are described to confirm the structure 15 proposed for nimbinone. The first, which leads to racemic O-methyl nimbinone [14], involves the polycyclization of a geraniol-derived intermediate 7. This same intermediate also afforded another preparation of (±)-methyl nimbiol [12]. The other synthesis starts from natural podocarpic acid and affords optically active O-methyl nimbinone [14]. Nimbinone [15] was recently described by Ira etal. (1) as one of the constituents of Azadirachta indica, the much studied "neem" tree. This skeleton is characterized by the methyl group at C-13, which suggests that the usual isopropyl residue has been degraded in the biosynthesis.Although the method is impractical if the aromatic ring carries too many substituents(2), the synthetic approach we adapted from the Livinghouse cascade cyclization (3) should permit the ready construction of nimbinone (Scheme 1). The suitably substituted phenylacetonitrile 5 was prepared in good yield (almost 50% overall) from o-methyl anisóle[1] via the 3-formyl derivative 2 (hexamethylenetetramine, CF3COOH; 75%), the primary alcohol 3 (NaBH4, MeOH, room temperature; 94%), the benzyl bromide 4 (PBr3, pyridine, room temperature; 81%) and finally the nitrile 5 (18-cr-6, KCN, MeCN, 60°; 71%). The latter was readily alkylated with geranyl bromide [6] to afford the racemic diene 7.Cyclization of the long sidechain in the normal manner (PhSOMe, BF3/MeN02) gave the trans-fused tricyclic 8. Transformation of C-7 and then C-3 to carbonyl groups by methods found effective in our previous syntheses aimed at candelabrone (2) afforded a racemic diketone 14, which showed identical spectral properties with the same 0methyl derivative of nimbinone described by Ira et al. (1).

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Synthesis of O-Methyl Nimbinone

Burnell¹,

Dumont²,

Théberge³

1993

J. Nat. Prod.

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“…Another synthesis of an A-ring functionalised compound, margocin (201), was reported by Burnell et al starting from dehydroabietic acid (2) via known allylic alcohol 69 (Scheme 26). 37 Allylic alcohol 69 was obtained with the route presented in Scheme 12 and also from the exocyclic olefin 22c, which was obtained from decarboxylation of dehydroabietic acid (2). Thus, the treatment of 2 with Pb(OAc) 4 gave a mixture of olefins in 50% yield, which after reaction with MCPBA the unreacted exocyclic olefin 22c could be separated in 35% yield.…”

Section: A N U S C R I P Tmentioning

confidence: 99%

“…The benzylic oxidation at C-7 is also characteristic of this skeleton (Schemes 6, 8,10, and 15-19), and the selective benzylic oxidation at C-15 has also been described (Scheme 19). The main synthetic strategy to build up the tricyclic ring system has been by large the intramolecular Friedel-Crafts cyclisation (Bogert-Cook reaction, see Schemes 31,32,[37][38][39][45][46][47][48]. This reaction has been part of a cationic polyene cyclisation sometimes, which even has been described enantioselectively (Scheme 36 and 53).…”

Section: Summary Of Key Reactionsmentioning

confidence: 99%

Aromatic abietane diterpenoids: total syntheses and synthetic studies

González

2015

Tetrahedron

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Simmons‐Smith Cyclopropanation Reaction

2001

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Almost 30 years after Emschwiller prepared IZnCH 2 I, Simmons and Smith discovered that the reagent formed by mixing a zinc‐copper couple with CH 2 I 2 in ether could be used for the stereospecific conversion of alkenes to cyclopropanes. Nowadays, the Simmons‐Smith cyclopropanation reaction is one of the most widely used reactions in the organic chemist's arsenal for the conversion of olefins into cyclopropanes. This popularity is mainly due to the stereospecificity of the reaction with respect to the double bond geometry and its compatibility with a wide range of functional groups. The chemoselectivity of the reaction toward some olefins is excellent and very few side reactions are observed with functionalized substrates. The metal carbenoid is electrophilic in nature and electron‐rich alkenes usually react much faster than electron‐poor alkenes. Furthermore, the ability to use proximal hydroxy or ether groups to dictate the stereochemical outcome of the CC bond forming process was recognized early on, and this unique property has been successfully exploited on numerous occasions. It has been recognized that halomethylmetal reagents are powerful synthetic tools for the stereoselective addition of a methylene unit to chiral acyclic allylic alcohols and allylic ethers. In addition, the use of halomethylzinc reagents in the presence of chiral additives is one of the few ways to cyclopropanate allylic alcohols efficiently and with good enantiocontrol. Carbenoids can be divided into the following two classes: (1) those of general structure MCH 2 X and (2) those corresponding to M = CH 2 . This chapter is focussed exclusively on the first class in which M = Zn, Sm, or Al. Although other metal carbenoids of type MCH 2 X, such as those derived from Cu, Cd, Hg, and In, have been reported to be effective reagents for the cyclopropanation of some olefins, they have been used only sporadically, and this review does not highlight these reactions. This chapter covers cyclopropanation reactions involving haloalkylzinc, aluminum, and samarium reagents published since the comprehensive chapter in Organic Reactions by Simmons that surveyed the literature up to 1973.

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Approaches to the Synthesis of Aromatic Diterpenes Oxygenated in the A Ring. Synthesis of Margocin

Abstract: The structure of margocin {24] is confirmed by its synthesis from useful synthons encountered during transformations exploring the utility of dehydroabietic acid as a chiral starting material for natural product synthesis.

Cited by 12 publications

References 18 publications

Synthesis of O-Methyl Nimbinone

Synthesis of O-Methyl Nimbinone

Aromatic abietane diterpenoids: total syntheses and synthetic studies

Simmons‐Smith Cyclopropanation Reaction

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