Homoannular Diene Research Articles

<b>Synthesis of 7-dehydrocholesterol through hexacarbonyl molybdenum catalyzed elimination reaction</b>

The efficiency of hexacarbonyl molybdenum catalyzed elimination reaction of the allylic acetates has been improved by the presence of O,N-bis(trimethylsilyl) acetamide in the reaction medium. The methodology is particularly well employed for the elimination of 7-acetoxycholesterol-3-acetate(cholestrol-3,7-diacetate) for which the resulting product obtained was exclusively 5,7-homoannular diene(7-dehydrocholesterol-3-acetate). Good yield is achieved (up to 70 %) while decreasing the side products formation and reducing the costs as compared to the previously used procedures. Hexacarbonyl molybdenum elimination reaction is greatly influenced by the reaction temperature, at low as well as at high temperature low yield of the homoannular diene product is separated while at moderate conditions of temperature high products formation is observed. KEY WORDS: Hexacarbonyl molybdenum, Elimination, Deacetoxylation, 7-Dehydrocholesterol, BSA Bull. Chem. Soc. Ethiop. 2011, 25(2), 247-254.

ChemInform Abstract: Synthesis of the Kopsia Alkaloids (.+-.)-11,12-Demethoxylahadinine B, (.+-.)-Kopsidasine and (.+-.)-Kopsidasine-N-oxide.

The key intermediate homoannular diene 10 was converted into (±)-11,12-demethoxylahadinine 6 via the conjugate reduction and oxidation of 15 with Mn(dpm)2/PhSiH3/O2 at 0°C. Oxidation of 14 with PhI(OAc)2/MeOH followed by reduction gave 17, which was converted into (±)-kopsidasine 19 and kopsidasine-N-oxide 20. The structure of the latter was confirmed by comparison with an authentic sample, and by X-ray crystallography.

Chromium‐Mediated Dearomatization: Application to the Synthesis of Racemic 15‐Acetoxytubipofuran and Asymmetric Synthesis of Both Enantiomers

AbstractAn efficient dearomatization process of [Cr(arene)(CO)3] complexes initiated by a nucleophilic acetaldehyde equivalent is detailed. It generates in a one‐pot reaction three CC bonds and two stereogenic centers. This process allowed a rapid assembly of a cis‐decalin ring system incorporating a homoannular diene unit in just two steps starting from aromatic precursors (Scheme 2). The method was applied to the total synthesis of the eudesmane‐type marine furanosesquiterpene (±)‐15‐acetoxytubipofuran (2). Two routes were successfully used to synthesize the γ‐lactone precursor of the furan ring. The key step in the first approach was a Pd‐catalyzed allylic substitution (Scheme 3), while in the second approach, an Eschenmoser–Claisen rearrangement was highly successful (Scheme 4). The Pd‐catalyzed allylic substitution could be directed to give either the (normal) product with overall retention as major diastereoisomer or the unusual product with inversion of configuration (see Table). For the synthesis of the (−)‐enantiomer (R,R)‐2 of 15‐acetoxytubipofuran, an enantioselective dearomatization in the presence of a chiral diether ligand was implemented (Scheme 7), while the (+)‐enantiomer (S,S)‐2 was obtained via a diastereoselective dearomatization of an arene‐bound chiral imine auxiliary (Scheme 8). Chiroptical data suggest that a revision of the previously assigned absolute configuration of the natural product is required.

Three Novel Triterpenoid Dienolides from Phyllanthus myrtifolius

Three novel pentacyclic triterpenoid dienolides, phyllenolide A (=3β-acetoxyglutina-5(10), 6-dien-27,8α-olide; 1), phyllenolide B (=3β-(benzoyloxy)glutina-5(10),6-dien-27,8α-olide; 2), and phyllenolide C (=3β-(2-hydroxybenzoyloxy)glutina-5(10),6-dien-27,8α-olide; 3), were isolated from the aerial parts of Phyllanthus myrtifolius Moon. (Euphorbiaceae). These three compounds possess an endocyclic γ-lactone moiety across ring C and a homo-annular diene system in ring B. Their structures were established by analyses of CD, NOED, and 2D-NMR spectra.

Synthesis of (±)-lahadinine B and (±)-11-methoxykopsilongine

6,7-Dimethoxytryptamine 11 was converted into the homoannular diene 19 which underwent a Diels–Alder reaction with acryloyl chloride to give 20. Subsequent radical decarboxylation in the presence of (PhSe) 2 provided 22, which was converted into (±)-lahadinine B 1 and (±)-11-methoxykopsilongine 2, thus confirming their structures.

Synthesis of the Kopsia alkaloids (±)-11,12-demethoxylahadinine B, (±)-kopsidasine and (±)-kopsidasine- N-oxide

The key intermediate homoannular diene 10 was converted into (±)-11,12-demethoxylahadinine 6 via the conjugate reduction and oxidation of 15 with Mn(dpm) 2/PhSiH 3/O 2 at 0°C. Oxidation of 14 with PhI(OAc) 2/MeOH followed by reduction gave 17, which was converted into (±)-kopsidasine 19 and kopsidasine- N-oxide 20. The structure of the latter was confirmed by comparison with an authentic sample, and by X-ray crystallography.

Studies on the synthesis of the indole alkaloids pauciflorine A and B

A double Bischler-Napieralski reaction of the 11-membered ring carbamate 15 gave the homoannular diene 17 in a single step.

3-Hydroxy-dihydrosantoninとTsOHの反応.Dihydrocotunolideの形式的合成

In connection with our another project a relatively large quantity of 5 was required. We, therefore, investigated the reaction of 3 with TsOH; this gave a diene mixture 7a, 7b, 6 and 5 in a ratio of 8:2:4:1. Almost the same 8:2:1 "equilibrium mixture" of the dienes 7a, 7b and 5 was also obtained when the purified samples of 5 and 7a were independently treated with TsOH under the same conditions. The above results suggest that the dienes might be produced in the following way; beta-elimination of H2O from 3 gives a homoannular diene 5. The protonation to the more electron-rich tetrasubstituted C4-C5 double bond of 5 from the less hindered alpha-side followed by the isomerization of the double bond gives 7a. 7b is formed via 7a and/or 5 by the double bond isomerizations. On the other hand, 6 is formed by concerted elimination of H2O between C3-OH and C6-H. As a result of these studies, the synthetic precursor of dihydrocostunolide 7b which was already prepared by Corey in 6 steps (ca. 7%) from santonin was synthesized in 3 steps (ca. 6%) from the latter.

Structural transformation of saikosaponins by gastric juice and intestinal flora.

Structural transformation of saikosaponin a and saikosaponin d, main components of Bupleuri Radix, were investigated using rat gastric juice (pH 1.5) and mouse intestinal flora in vitro and the excretion of saikosaponin derivatives in rat feces was also studied. Quantitative analysis of saikosaponins and their derivatives was carried out by high performance liquid chromatography. By the incubation of saikosaponins in rat gastric juice, saikosaponin a decreased with time dependently. After 3 h, saikosaponin a disappeared completely and saikosaponin b1 which possessed heteroannular diene moiety at C-11,13(18) and saikosaponin g which possessed homoannular diene moiety at C-9(11),12 were detected with the ratio of 3:1. On the other hand, saikosaponin d rapidly changed to only saikosaponin b2 (heteroannular diene structure) completely 30 min after the incubation. Next, by the anaerobic incubation of saikosaponin a with mouse intestinal flora, the formation of saikogenin F, a genuine aglycone of saikosaponin a, reached to the maximum 1 h after the incubation and its yield was 80%. A minor peak of prosaikogenen F, a monofucoside of saikogenin F, was also detected at 15 min. By the same procedures, saikosaponin b1, g, d and b2 also changed to the corresponded prosaikogenin A, H, G and D and saikogenin A, H, G and D with the almost similar pattern to that of saikosaponin a. Finally, the contents of nine excreted metabolites from saikosaponin a, 5 and 20 mg/kg, in feces after its oral administration was investigated using fasted or non-fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

New derivatives of saikosaponins.

In the course of studies on the metabolism of saikosaponins, which are the main constituents of Bupleurum falcatum L., five new compounds derived from saikosaponins a, c and d were isolated after incubation with acid and snail enzyme. On incubation of saikosaponins a and c at 60°C in a 1 N sulfuric acid-dioxane solution, saikosaponins g and i possessing a homoannular diene moiety at C-9 (11), 12 were isolated, and their structures were elucidated as 3β, 16β, 23, 28-tetrahydroxyoleana-9 (11), 12-diene 3-O-β-D-glucopyranosyl-(1→3)-β-D-fucopyranoside and 3β, 16β, 28-trihydroxyoleana-9 (11), 12-diene 3-O-β-D-glucopyranosyl-(1→6)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside, respectively. Furthermore, on incubation of saikosaponins b1, g and b2 with snail enzyme for 12h at 37°C, prosaikogenins A, H, and D were formed ; they were identified as the 3-β-D-fucopyranosides of saikogenins A, H and D.

Conformational studies. Part 3. Synthesis of some alicyclic dienes

(+)-trans-1,2,3,4,4a,8a-Hexahydro-4a-methylnaphthalene, cholesta-1,3-diene, and cholesta-1,3,7-triene have been synthesised by standard methods. These chiral, cisoid, homoannular dienes exhibit o.r.d. curves of sign in agreement with the predictions of the Chiral Diene Rule.

Reactions of Ring C in Glycyrrhetic Acid Derivatives

AbstractThe chemistry of the relatively unreactive glycyrrhetic acid (1) ring C was investigated. The enone group in this ring was reduced by diborane to allylic alcohols (6, 7), which can be readily converted into the corresponding homoannular dienes (2, 5). These dienes were also prepared by NaBH4 reduction of the enone group. The epoxidation of the diene 2 leads to the mono‐(12) and di‐(14) epoxides. A new ring C enone system (13) was also obtained. Treatment of the two different tosylhydrazones derivatives (16, 20) with methyllithium gave the conjugated methylene compounds (17, 21). The NMR spectrum of the latter compound was also studied with a shift reagent — Eu(FOD). The mass spectra of the homoannular dienes (2, 5), allylic alcohols (6, 7) and 11‐methylene compounds (17, 21) were studied and some new types of fragmentation were suggested.

ChemInform Abstract: FLUORINATION STUDIES ON GLYCYRRHETIC ACID DERIVATIVES

Attempts to introduce a fluorine atom directly at the C-3 position of the triterpenoidal glycyrrhetic acid 1 by reacting the tosylate 2 with KF, or methyl glycyrrhetate 5 with Et2NCF2CHCIF, failed. The ring A olefin 3 and the rearrangement product 4 were obtained. The homoannular diene 7 was treated with NOF, but only nitroso-fluorine compounds 8, 9 were isolated. Nitrosyl fluoride was also reacted with olefin 3. A difluoro compound 10 and the expected 2-keto-3α-fluoro compound 11 were obtained. The above two olefins were also reacted with bromine fluoride. Although the diene 7 gave only fluorine-free compounds 13, 14, the expected fluoro-bromine compound 16 was obtained from 3. When the 2β-fluoro-3α-bromo compound was treated with Bu3SnH, the bromine atom was replaced by hydrogen and the 2β-fluoro compound 17 was formed.

Fluorination Studies on Glycyrrhetic Acid Derivatives

AbstractAttempts to introduce a fluorine atom directly at the C‐3 position of the triterpenoidal glycyrrhetic acid 1 by reacting the tosylate 2 with KF, or methyl glycyrrhetate 5 with Et2NCF2CHCIF, failed. The ring A olefin 3 and the rearrangement product 4 were obtained. The homoannular diene 7 was treated with NOF, but only nitroso‐fluorine compounds 8, 9 were isolated. Nitrosyl fluoride was also reacted with olefin 3. A difluoro compound 10 and the expected 2‐keto‐3α‐fluoro compound 11 were obtained. The above two olefins were also reacted with bromine fluoride. Although the diene 7 gave only fluorine‐free compounds 13, 14, the expected fluoro‐bromine compound 16 was obtained from 3. When the 2β‐fluoro‐3α‐bromo compound was treated with Bu3SnH, the bromine atom was replaced by hydrogen and the 2β‐fluoro compound 17 was formed.

The Cotton Effects of Conjugated Homoannular Dienes. I. The Non-generality of the Rule of Moscowitz

The non-generality of the diene rule of Moscowitz, relating the helicity of a non-planar conjugated homoannular diene to the sign of its Cotton effect, is discussed. We report the preparation of 3β-bromoacetoxy-16α-ethyl-162-cyano-162,21-cyclo-5α-pregna-17,21-diene, the X-ray crystallographic analysis of which confirms, as reported by Ahmed and Pollard, the stereochemistry which we previously assigned to the parent alcohol and acetate. We also report the synthesis of the methyl ketonic analogues of these dienonitriles and show that their sodium borohydride reduction product still has a Cotton effect in contradiction to the diene rule. The implications of these and other experiments are discussed.

Synthesis of polyimides by photoaddition of bismaleimides to benzene

AbstractPolyimides have been synthesized by the sensitized photoaddition of aliphatic and aromatic bismaleimides to benzene. The reaction involves 2+2 cycloaddition to give homoannular diene intermediate followed by Diels‐Alder addition to give polymer. Proof of structure is based mainly on a comparison of infrared spectra with those of the corresponding polyimides prepared from maleic anhydride‐benzene photoadduct and diamines. The very low solubility of the polymers indicates that crosslinking probably occurred during photolysis. All the polyimides appear to decompose by decyclization at about 420–485°C. Polymer yield was dependent on bismaleimide structure.

Inverse sign of the chiral-optical effects of non-planar heteroannular cisoid dienes

The chiral-optical effects of heteroannular cisoid dienes are attributed to the dissymmetry of the skewed diene chromophore as in the case of homoannular cisoid dienes and of transoid dienes. The sign of these effects for a small number of heteroannular cisoid dienes is opposite to that predicted from the “diene rule” (1). This inversion of sign is ascribed to the change in electronic properties of the diene when, as in these compounds, the dihedral angle about the central bond is very large compared to that of the homoannular dienes. Consistent with these observations, recent theoretical treatments of the functional dependence of the rotatory strengths on the dihedral angle demonstrate that the sign of the CD and ORD effects can change at large angles.

Triterpenoids from bupleurum falcatum L.—II : Isolation of saikogenin B and longispinogenin

A new triterpenoid triol having a homoannular diene together with the known longispinogenin have been isolated, as minor components, by acid hydrolysis of the saponin from the roots of Bupleurum falcatum L. The new triol, saikogenin B, has been shown to have the structure olean-9(11),12-diene-3β,16β,28-triol. In the course of the structure elucidation, the epimeric 11-OH derivatives of longispinogenin were prepared and the results compared with those described for β-amyrin.

Triterpenoids from bupleurum falcatum L.—I : The structure of saikogenins A, C and D

The saponin from the roots of Bupleurum falcatum L. on acid hydrolysis affords three triterpenes containing a heteroannular diene and an unidentified triterpene fraction which shows a homoannular diene chromophore. The structures of the three heteronnular dienes, saikogenins A, C and D, have been shown to be olean-11,13(18)-diene-3β,16β,23,28-tetrol (Ia), -3β,16β,28-triol (IIa) and -3β,16α,23,28-tetrol (IIIa), respectively.

Raney nickel desulfurization of 19-norsteroid ethylenethioketals : Synthesis of 4-estrene-2, 17-dione and related compounds

The synthesis of 4-estrene-2,17-dione (VIII) is described. Raney nickel desulfurization of the dihydroxy ethylenethioketal (IV) resulted in the dihydroxy compound (VI) with concomitant oxidation of the 2α-hydroxy function to give in low yield the corresponding 2-keto product (V). Further, it has been observed that Raney nickel desulfurization of the diacetoxy ethylenethioketal compound (III) under similar conditions eliminated the 2α-acetoxy group to give exclusively the homoannular diene (X), which on mild treatment with acid, isomerized to the heteroannular diene (XII).