Rogiolenyne A,B, and C: The First Branched Marine C15 Acetogenins. Isolation from the Red Seaweed Laurencia microcladia or the Sponge Spongia zimocca of II Rogiolo

It is shown here that the red seaweed Laurencia microcladia, collected off the torrent II Rogiolo, south of Livorno, contains rogiolenyne A (= (?)-(1R*,2S*,3R*,5S*,7S*)-2-(bromomethyl)-5-[(Z)-1-chlorohex-3-en-5-ynyl]-3-ethyl-4,8-dioxabicyclo[5.1.0]octane; (?)- 1 ) while the sponge Spongia zimocca, which grows in the same small area, contains rogiolenyne B (= (?)-(2R*3R*,4R*,5R*,7S*)-3-(bromomethyl)-5-chloro-7-[(Z)-1-chlorohex-3-en-5-ynyl]-2-ethyloxepan-4-ol; (?)- 4a ) and its acetate, rogiolenyne C((?)- 4b ). These structures, which are based on extensive NMR and MS data and on chemical transformation, are the first examples of branched marine C₁₅ acetogenins. Biogenesis of (?)- 1 in L. microcladia is thought to involve C(12) extrusion form a C₁₅ linear tetraen-1-yne precursor via H⁺-induced cyclopropane ring closure, followed by Br⁺-induced cyclopropane ring opening, aided by C–O^? attack (Scheme 2). It is also proposed that transfer of (?)- 1 to S. zimocca is followed by epoxide ring opening by Cl^? to give (?)- 4a and acetylation to give (?)- 4b .     

Stereoselective Conversion of Campholene- to Necrodane-Type Monoterpenes. Novel Access to (−)-(R,R)- and (R,S)-α-Necrodol and the Enantiomeric γ-Necrodols

Naturally occurring (?)-(R,R)-α-necrodol ((?)- 1 ) and its C(4)-epimer (?)- 2 are obtained in 84 and 44% yields, respectively, by lithium ethylenediamide (LEDA) treatment of the corresponding β-necrodols (?)- 3 and (?)- 4 (Scheme 1, Table), both readily available from (?)-campholenyl acetate ((?)- i ) by an efficient stereoselective synthesis. The thermodynamically preferred (?)-(R)-γ-necrodol ((?)- 5 ) becomes the major product (≥ 80% yield) after either prolonged treatment with LEDA or exposure of α- and β-necrodols to BF₃·Et₂O. In an alternative route, (+)- 5 is prepared starting from (+)-campholenal ((+)- ii ) via Pd-catalysed decarbonylation to (?)-(S)-1,4,5,5-tetramethylcyclopent-l-ene ((?)- 6 ) and subsequent application of an acid-catalysed CH₂O-addition/rearrangement sequence (Scheme 2).     

Enantioselective Synthesis of 3- Azabicyclo[4.3.0]nonane Alkaloids

The stereospecific synthesis of the monoterpene alkaloids (?)-α-skytanthine ((?)- 2 ), (?)-N -demethyle-δ-sky-tanthine((?)- 7 ), and (+)-epidihydrotecomanine (+)- 4 was achieved from a common intermediate 22 , which in turn was obtained from (1R,4S,1′S)-2-(1′-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene (10) ,via a ketene aza-Claisen rearrangement. The piperidine derivative (+)- 31 , formally the aza-analogue of (+)-isoiridomyrmecin, was also obtained from the same intermediate 22 .     

Total Syntheses of (−)-Conduritol B ((−)-1L-Cyclohex-5-ene-1,3/2,4-tetrol) and of (+)-Conduritol F((+)-1D-Cyclohex-5-ene-1,2,4/3-tetrol). Determination of the Absolute Configuration of (+)-Leucanthemito

The ‘naked sugar’ (+)-(1R,2R4R)-2-endo-cyano-7-oxabicyclo[2.2.1]hept-5-sn-2-exo-yl acetate ((+)- 4 ) was converted (7 steps, 45% overall) with high stereoselectivity into (?)-(4R,5S,6R)-4,5,6-tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-2-en-1-one ((?)- 11 ). Reduction of (?)- 1 with NaBH₄- CeCl₃ · 7 H₂O, followed by deprotection of the silyl ether moieties gave (+)-conduritol F ((+)- 1 ; 47%) whose characteristics were identical to those of natural (+)-leucanthemitol. Reduction of (?)- 11 with DIBAH, followed by deprotection of the silyl ether moiety led to (?)-conduritol B ((?)- 3 ; 51 %).     

Synthese und Chiralität der stereoisomeren Achillene,Achillenole und Hymentherene

(+)-cis-Achillene ( 10 ) and (?)-trans-achillenol (7), two monoterpenes recently isolated [1] from the essential oil of Achilleafilipendulina, were synthesized, together with their stereoisomers (?)-(9) and (+)-(8), starting from (S)-(+)-2,6-trans-dimethylocta-1,3, 7-triene ( 1 ). The isomeric ß-hymen thereties ((?)- 3 and (+)-4), often quoted [2] [3] [4] but never isolated, were obtained as intermediates. The mode of synthesis chosen establishesis (R)-chirality for naturally occurring (?)-trans-achillenol (7) and (+)-cis-achillene ( 10 ) as well as for the purely synthetic 4, 7-diene derivatives described in this paper.     

Circular Dichroism of Tricarbonyl(diene)iron Complexes. The Octant Rule Applied to Ketones Perturbed by Remote Fe(CO)3 Groups. Crystal Structure of (±)-Tricarbonyl[(1RS,4RS,5RS,6SR)-C5,6,C-η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron

The preparation and the CD spectra of optically pure (+)-trans-μ-[(1R,4S,5S,6R,7R,8S)-C,5,6,C -η : C,7,8,C-η-(5,6,7,8-tetramethylidene-2-bicyclo [2.2.2]octanone)]bis(tricarbonyliron) ((+)- 7 ) and (+)-tricarbonyl[(1S,4S,5S,6R)-C-5,6,C-η-(5,6,7,8,-tetramethylidene-2-bicyclo[2.2.2]octanone)]iron ((+)- 8 ), and of its 3-deuterated derivatives (+)-trans-μ-[(1R,3R,4S,5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C-η-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]-(octanone)]bis(tricarbonyliron) ((+)- 11 ) and (+)-tricarbonyl[(1S,3R,4S,5S,6R)-C-5,6,C- η-(5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone)]iron ((+)- 12 ) are reported. The chirality in (+)- 7 and (+)- 8 is due to the Fe(CO)₃ moieties uniquely. The signs of the Cotton effects observed for (+)- 7 and (+)- 8 obey the octant rule (ketone n→π*_CO transition). Optically pure (?)-3R-5,6,7,8-tetramethylidene(3-D)-2-bicyclo[2.2.2]octanone ((?)- 10 ) was prepared. Its CD spectrum showed an ‘anti-octant’ behaviour for the ketone n→π*_CO transition of the deuterium substituent. The CD spectra of the alcoholic derivatives (?)-trans-μ-[(1R,2R,4S, 5S,6R,7R,8S)-C,5,6,C-η : C,7,8,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]bis(tricarbonyliron) ((?)- 2 ) and (?)-tricarbonyl- [(1S,2R,4S,5S,6R)- C,5,6,C- η-(5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octanol)]iron ((?)- 3 ) and of the 3-denterated derivatives (?)- 5 and (?)- 6 are also reported. The CD spectra of the complexes (?)- 2 , (?)- 3 , (+)- 7 , and (+)- 8 were solvent and temperature dependent. The ‘endo’-configuration of the Fe(CO)₃ moiety in (±)- 8 was established by single-crystal X-ray diffraction.     

Synthesis of the Enantiomerically Enriched Macrocyclic Lactones (+)-(S)- and (−)-(R)-Phoracantholide I and (+)-(S)-Tetradecan-13-olide

Synthesis of two naturally occurring macrocyclic lactones is described. (?)-(R)-Phoracantholide I ((?)- 1 ; Scheme 2) was synthesized by asymmetric and chemoselective reduction of the side-chain C?O group of (?)4-(1-nitro-2-oxocyclohexyl)butan-2-one ((?)- 6 ) with (R)-Alpine-Hydride (47% ee). It was shown that the formation of only one diastereoisomer of the hemiacetal 5 , by methylation with (i-PrO)₂TiMe₂ of ketoaldehyde (?)- 2 is thermodynamically controlled. (+)-(S)-Tetradecan-13-olide ((+)- 10 ) was obtained by reduction of diketone (±)- 11 with optically active borohydrides followed by denitration (Scheme 3).     

Photochemische Umsetzung von optisch aktiven 2-(1′-Methylallyl)anilinen mit Methanol

Photochemical Reaction of Optically Active 2-(1′-Methylallyl)anilines with Methanol It is shown that (?)-(S)-2-(1′-methylallyl)aniline ((?)-(S)- 4 ) on irradiation in methanol yields (?)-(2S, 3R)-2, 3-dimethylindoline ((?)-trans- 8 ), (?)-(1′R, 2′R)-2-(2′-methoxy-1′-methylpropyl)aniline ((?)-erythro- 9 ) as well as racemic (1′RS, 2′SR)-2-(2′-methoxy-1′-methylpropyl) aniline ((±)-threo- 9 ) in 27.1, 36.4 and 15.7% yield, respectively (see Scheme 3). By deamination and chemical correlation with (+)-(2R, 3R)-3-phenyl-2-butanol ((+)-erythro- 13 ; see Scheme 4) it was found that (?)-erythro- 9 has the same absolute configuration and optical purity as the starting material (?)-(S)- 4 . Comparable results are obtained when (?)-(S)-N-methyl-2-(1′-methylallyl)aniline ((?)-(S)- 7 ) is irradiated in methanol, i.e. the optically active indoline (+)-trans- 10 and the methanol addition product (?)-erythro- 11 along with its racemic threo-isomer are formed (cf. Scheme 3). These findings demonstrate that the methanol addition products arise from stereospecific, methanol-induced ring opening of intermediate, chiral trans, -(→(?)-erythro-compounds) and achiral cis-spiro [2.5]octa-4,6-dien-8-imines (→(±)-threo-compounds; see Schemes 1 and 2).     

Synthesis of (+)-1,3:2,5-dianhydroviburnitol ((+)-(1R,2R,3S,5R,6S)-4,7-dioxatricyclo[3.2.1.03,6]octan-2-ol)

Epoxidation of (?)-(1R,2R,4R)-2-endo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl acetate ((?)-5) followed by saponification afforded (+)-(1R,4R,5R,6R)-5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one ((+)-7). Reduction of (+)-7 with diisobutylaluminium hydride (DIBAH) gave (+)-1,3:2,5-dianhydroviburnitol ( = (+)-(1R,2R,3S,4R,6S)-4,7-dioxatricyclo[3.2.1.0^3,6]octan-2-ol; (+)-3). Hydride reductions of (±)-7 were less exo-face selective than reductions of bicyclo[2.2.1]heptan-2-one and its derivatives with NaBH₄, AlH₃, and LiAlH₄ probably because of smaller steric hindrance to endo-face hydride attack when C(5) and C(6) of the bicyclo-[2.2.1]heptan-2-one are part of an exo oxirane ring.     

Total Synthesis of L-Allose,L-Talose,and derivatives.

(1S, 4R, 5S, 6S)-5-exo, 6-exo-(Isopropylidenedioxy)-7-oxabicyclo[2.2.1]heptan-2-one ((?)- 1 ) was transformed with high stereoselectivity to L -allose. Similarly, enantiomer (+)- 1 was transformed into L -talose. The ketones (+)- 1 and (?)- 1 were derived from furan and 1-cyanovinyl (1S)-camphanate and 1-cyanovinyl (1R)-camphanate, respectively.     

Acid-Catalyzed [3,3]-Sigmatropic Rearrangements of N-Propargylanilines

The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)-, N-(1′-methylprop-2′-ynyl)-, and N-(1′-arylprop-2′-ynyl)-2,6-, 2,4,6-, 2,3,5,6-, and 2,3,4,5,6-substituted anilines in mixtures of 1N aqueous H₂SO₄ and ROH such as EtOH, PrOH, BuOH etc., or in CDCl₃ or CCl₄ in the presence of 4 to 9 mol-equiv. trifluoroacetic acid (TFA)has been investigated (cf. Scheme 12-25 and Tables 6 and 7). The rearrangement of N-(3′-X-1′,1′-dimethyl-prop-2′-ynyl)-2,6- and 2,4,6-trimethylanilines (X = Cl, Br, I) in CDCl₃/TFA occurs already at 20° with τ_1/2 of ca. 1 to 5 h to yield the corresponding 6-(1-X-3′-methylbuta-1,2′-dienyl)-2,6-dimethyl- or 2,4,6-trimethylcyclohexa-2,4-dien-1-iminium ions (cf. Scheme 13 and Footnotes 26 and 34) When the 4 position is not substituted, a consecutive [3,3]-sigmatropic rearrangement takes place to yield 2,6-dimethyl-4-(3′-X-1′,1′-dimethylprop-2′-ynyl)anilines (cf. Footnotes 26 and 34). A comparable behavior is exhibited by N-(3′-chloro-1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ( 45 ., cf. Table 7). The acid-catalyzed rearrangement of the anilines with a Cl substituent at C(3′) in 1N aqueous H₂SO₄/ROH at 85-95°, in addition, leads to the formation of 7-chlorotricyclo[3.2.1.0^2,7]oct-3-en-8-ones as the result of an intramolecular Diels-Alder reaction of the primarily formed iminium ions followed by hydrolysis of the iminium function (or vice versa; cf. Schemes 13,23, and 25 as well as Table 7). When there is no X substituent at C(1′) of the iminium-ion intermediate, a [1,2]-sigmatropic shift of the allenyl moiety at C(6) occurs in competition to the [3,3]-sigmatropic rearrangement to yield the corresponding 3-allenyl-substituted anilines (cf. Schemes 12,14–18, and 20 as well as Tables 6 and 7). The rearrangement of (?)?(S)-N-(1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 38 ; cf. Table 7) in a mixture of 1N H₂SO₄/PrOH at 86° leads to the formation of (?)-(R)-3-(3′-phenylpropa-1′,2′-dienyl)-2,6-dimethylaniline ((?)- 91 ), (+)-(E)- and (?)-(Z)-6-benzylidene-1,5-dimethyltricyclo[3.2.1.0^2′7]oct-3-en-8-one ((+)-(E)- and (?)-(Z)- 92 , respectively), and (?)-(S)-2,6-dimethyl-4-( 1′-phenylprop-2′-ynyl)aniline((?)- 93 ). Recovered starting material (10%) showed a loss of 18% of its original optical purity. On the other hand, (+)-(E)- and (?)-(Z)- 92 showed the same optical purity as (minus;)- 38 , as expected for intramolecular concerted processes. The CD of (+)-(E)- and (?)-(Z)- 92 clearly showed that their tricyclic skeletons possess enantiomorphic structures (cf. Fig. 1). Similar results were obtained from the acid-catalyzed rearrangement of (?)-(S)-N-(3′-chloro-1′phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 45 ; cf. Table 7). The recovered starting material exhibited in this case a loss of 48% of its original optical purity, showing that the Cl substituent favors the heterolytic cleavage of the N–C(1′) bond in (?)- 45. A still higher degree (78%) of loss of optical activity of the starting aniline was observed in the acid-catalyzed rearrangement of (?)-(S)-2,6-dimethyl-N-[1′-(p-tolyl)prop-2′-ynyl]aniline ((?)- 42 ; cf. Scheme 25). N-[1′-(p-anisyl)prop-2-ynyl]-2,4,6-trimethylaniline( 43 ; cf. Scheme 25) underwent no acid-catalyzed [3,3]-sigmatropic rearrangement at all. The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)aniline ( 25 ; cf. Scheme 10) in 1N H₂SO₄/BuOH at 100° led to no product formation due to the sensitivity of the expected product 53 against the reaction conditions. On the other hand, the acid-catalyzed rearrangement of the corresponding 3′-Cl derivative at 130° in aqueous H₂SO₄ in ethylene glycol led to the formation of 1,2,3,4-tetrahydro-2,2-dimethylquinolin-4-on ( 54 ; cf. Scheme 10), the hydrolysis product of the expected 4-chloro-1,2-dihydro-2,2-dimethylquinoline ( 56 ). Similarly, the acid-catalyzed rearrangement of N-(3′-bromo-1′-methylprop-2′-ynyl)-2,6-diisopropylaniline ( 37 ; cf. Scheme 21) yielded, by loss of one i-Pr group, 1,2,3,4-tetrahydro-8-isopropyl-2-methylquinolin-4-one ( 59 ).     

Synthesis of the Bretonins,Polyolefinic Esterified Glyceryl Ethers of an Unidentified Sponge from the North-Brittany Sea: Absolute Configuration and Novel Structure Assignment

The absolute configurations of acetylated bretonin A (= (+}-( R )-1-[(acetoxy)methyl]-2-{[(4E,6E,8E)-dodeca-4,6,8-trienyl]oxy}ethyl 4-acetoxybenzoate; (?)- 1b ) and isobretonin A (= (+)-(S)-3-{[(4E,6E,8E)-do-deca-4,6,8-trienyl]oxy}-2-hydroxypropyl 4-hydroxybenzoate; (+)-2), previously isolated from an undetermined sponge of the North Brittany sea, were established by comparison with synthetic (+)- lb and (+)- 2 , obtained from the condensation of commerical (?)-(R)-2,2-dimethyl-1,3-dioxolan-4-yl p-toluenesuifonate ((?)-(R)- 15 ) with a mixture of (4E,6E,8E)- ( 14e ) and (4E,6Z,8E)-dodeca-4,6,8-trien-1-ol ( 14z ). This also allowed confirming the structure and configuration of bretonin B (= (S)-2-{[(4E,6Z,8E)-dodeca-4,6,8-trienyl]oxy}-1-(hydroxy-methyl)ethyl 4-hydroxybenzoate; 3 ) which was also isolated from the same sponge, albeit in a too small amount for a complete study. As concerns the glyceryl ethers precursors of the bretonins, co-occurrence of the usual (S)-con-figuration (from 1a ) with the unusual (R)-configuration (from (+)- 2 )) poses intriguing biogenetic problems.     

Synthese des Dysidins

Synthesis of Dysidin The synthesis of dysidin ((?)- 1 ), the enantiomer of a metabolite of the marine sponge Dysidea herbacea, is described. To effect the synthesis, (±)-5-isopropyl-4-methoxy-3-pyrrolin-2-one ( 7 ) is converted to its lithium salt and reacted with (?)-(5R,2E)-3-methoxy-5-trichloromethyl-2-hexenoyl chloride ((-)- 11 ) to give (?)- 1 and its diastereoisomer (+)-5-epidysidin ((+)- 12 ) epimeric at C(5) of the pyrrolinone ring. The (?)-acyl chloride (?)- 11 has been synthesized from (+)-(R)-3-(trichloromethyl)butanoic acid ((+)- 8 ) via the intermediates (+)- 9 and (?)- 10 , the pyrrolinone 7 from N-benzyl-oxycarbonyl-L-valine via the intermediate 5 . The enantiomers of acid 8 have been resolved by fractional crystallization of their diastereoisomeric N-(1-phenylethyl)amides. The (R)-chirality of (+)- 8 was determined by comparing the ¹H-NMR spectra of the diastereoisomeric N-(1-phenylethyl)amides 16 and 17 , made from (+)- 8 by substituting deuterium for chlorine, with the spectra of the N-(1-phenylethyl)amides 14 and 15 of known absolute configuration. This correlation shows that literature value (R) for (?)- 8 is in error. Therefore, the structural formulae of (?)-dysidenin and (+)-isodysidenin, two other metabolites of D.herbacea, have to be changed to their mirror images as shown in formulae (?)- 3 and (+)- 4 , respectively.     

A New Total Synthesis of D-threo-L-talo-Octose

A new approach to the total, asymmetric synthesis of D -threo-L -talo-octose ((?)- 1 ) and its derivatives is presented. It is based on the chemoselective Wittig-Horner monoolefination of a 5-deoxy-D -ribo-hexodialdose derivative 4 obtained by selective reduction of (?)-5-deoxy-2.3-O-isopropylidene-/β-D -ribo-hexofuranurono-6,1-lactone ((?)- 3 ). Allylic bromination of the resulting methyl (E)-oct-6-enofuranuronate (+)- 5 followed by intramolecular nucleophilic displacement of the so-obtained bromides gave a 13.3:1 mixture of (?)-methyl (E)-l,4-anhydro-6,7-dideoxy-2,3-O-isopropylidene-β-L -talo-oct-6-enopyranuronate ((?)- 8 ) and methyl (E)-l,4-anhydro-6,7-dideoxy-2,3-O-isopropylidene-α-D -allo-oct-6-enopyranuronate ( 9 ). The double hydroxylation of the enoate (?)- 8 followed Kishi's rule and gave the corresponding D -threo-β-L -talo-octopyranuronate derivative (?)- 11 with a good diastereoselectivity. Reduction of ester (?)- 11 and deprotection led to pure (?)- 1 .     

Synthesis of Aristotelia-Type Alkaloids. Part XII. Total synthesis of (−)-tasmanine. Stereoelectronic factors that control the rearrangement of 3H-indol-3-ol derivatives to oxindoles ( = 1,3-dihydro-2H-indol-2-ones) or to pseudoindoxyls ( =1,2-dihydro-3H-indol-3-ones)

The oxidative transformation of (+)-aristoteline ((+)- 5 ) into its metabolites, the recently synthesized indole alkaloids (?)-serratoline ((?)- 6 ), (+)-aristotelone ((+)- 2 ), and (?)-alloaristoteline ((?)- 22 ), was investigated in more detail. It was demonstrated that the diastereoface selectivity of the reaction of (+)- 5 with 3-chloroperbenzoic acid can be altered by variation of the solvent as well as by addition of CF₃COOH. The chemoselectivity of the 1,2-rearrangement of the intermediate 3H-indol-3-ol derivatives could be controlled as follows: treatment of 3H-indol-3-ols with aqueous polyphosphoric acid led to the pseudoindoxyl ( = 1,2-dihydro-3H-indol-3-one) derivatives, whereas an analogous treatment of the corresponding O-benzoates furnished exclusively the corresponding, constitutionally isomeric 2-oxindole ( = 1,3-dihydro-2H-indol-2-one) products. Exploitation of these and related findings led to efficient total syntheses of the Aristotelia alkaloid (?)-tasmanine ((?)- 1 ) and of the corresponding unnatural epimer (+)- 12 , as well as of the two pseudoindoxyls (+)-aristotelone ((+)- 2 ) and (?)-2-epiaristotelone ((?)- 11 ). All these transformations were carried out with synthetic (+)-aristoteline ((+)- 5 ) as the single indole alkaloid precursor.     

Synthesis of (−)-Conduritol C (1L-Cyclohex-5-ene-1,2,3/4-tetrol)

(1R, 2R, 4R)-2-endo-Cyano-7-oxabicyclo[2.2.1]hept-5-en-2-yl acetate ((?)-7) has been transformed into the all-cis-configurated 4L -4,5,6/0-trihydroxycyclohex-2-en-1-one derivatives (?)- 12 and (?)- 19 . (?)-Conduritol C ((?)- 3 ) was derived in a stereospecific manner from (?)- 12 .     

A Novel,Degraded Polyketidic Lactone,Leptosphaerolide, and Its Likely Diketone Precursor,Leptosphaerodione. Isolation from Cultures of the Marine Ascomycete Leptosphaeria oraemaris (LINDER)

Acetone extraction of cultures of the marine ascomycete Leptosphaeria oraemaris (LINDER) on cornmeal disk gave the novel polyketide derivative leptosphaerolide ( = (+)-7-[(1E)-l,3-dimethylpent-1-enyl]-10-hydroxy-3-methoxybenzo[1,2-b:5,4-c′]dipyran-2(9H)-one; (4+)-8) besides the o-dihydroquinone 3-[(1E)-1,3-dimethylpent-1-euyl]-8,10-dihydroxy-7-methoxy-8-(2-oxopropyl)-1H-naphtho[2,3-c]pyran-9(8H)-one ( 1 ) as a 10:9 mixture of epimers. retro-Aldol reaction of 1 gave leptosphaerodione ( = (?)-3-[(1E)-1,3-dimethylpent-1-enyl]-10-hydroxy-7-methoxy-1H-naphtho[2,3-c]pyran-8,9(8H)-dione; (?)-6) which was also present in small amounts in the extracts and which gave 1 on reaction with acetone. It is thus likely that 1 is an artefact of the extraction by acetone. Biogenetically (+)-8 might derive from (?)-6 via an unusual oxidation with loss of CO₂.     

Preparation of optically active flowery and woody-like odorant ketones via Corey-Chaykovsky oxiranylation: Irones and analogues

α-, β-, and γ-Irones and analogues have been prepared from optically active ketones (+)- 1 , (+)- 6a,b , and (+)- 17 , via a Corey-Chaykovsky oxiranylation (Me₂S, Me₂SO₄, Me₂SO, NaOH) followed by isomerisation (SnCl₄ or MgBr₂). (+)-Dihydrocyclocitral ( 19a ), obtained from (?)-citronellal, and analogue (+)- 19b , were condensed with various ketones to afford (+)- 21a–f , and after hydrogenation (+)- 22a–f. A mild oxidative degradation of aldehydes (+)-trans-and (?)-cis- 8a,b , to ketones (?)- 16a,b , as well as olfactive evaluations, ¹³C-NMR assignments, and absolute configurations of the intermediate epoxides, aldehydes, and alcohols are presented.     

Reactions of Allyl Alcohols of the Pinane Series and of Their Epoxides in the Presence of Montmorillonite Clay

The reactivity of allyl alcohols of the pinane series and of their epoxides in the presence of montmorillonite clay in intra‐ and intermolecular reactions was studied. Mutual transformations of (+)‐trans‐pinocarveol ((+)‐ 2 ) and (?)‐myrtenol ((?)‐ 3a ) were major reactions of these compounds on askanite–bentonite clay (Schemes 1 and 2). However, the two reactions gave different isomerization products, indicating that the reactivity of the starting alcohol (+)‐ 2 or (?)‐ 3a was different from that of the same compound (+)‐ 2 or (?)‐ 3 formed in the course of the reactions. (?)‐cis‐ and (+)‐trans‐Verbenol ((?)‐ 16 and (+)‐ 12 , resp.), as well as (?)‐cis‐verbenol epoxide ((?)‐ 20 ) reacted with both aliphatic and aromatic aldehydes on askanite–bentonite clay giving various heterocyclic compounds (Schemes 4, 5 and 7); the reaction path depended on the structure of both the terpenoid and the aldehyde.     

Synthesis of Polypropionate Fragments Containing Tertiary-Alcohol Moieties. Cross-aldolisations with lithium enolates of 7-oxabicyclo[2.2.1]heptan-2-one derivatives

The Diels-Alder adduct of 2,4-dimethylfuran to 1-cyanovinyl (1′R)-camphanate ((+)-(1R,2S,4R)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′R)-camphanate ((+)- 1 )) was converted into (+)-2,7-dideoxy-2,4-di-C-methyl-L -glycero- ((+)- 6 ) and -D -glycero-L -altro-heptono-1,4-lactone ((+)- 7 ), into (?)-(3R,4R,5R,6S)-3,4:5,7-bis(isopropylidenedioxy)-4,6-dimethylheptan-2-one ((?)- 22 ), and into (+)-(2R,3R,4R,5S,6S)-3,4:5,6-bis(isopropylidenedioxy)-2,4-dimethylheptanal ((+)- 34 ). Condensation of ((+)- 34 with the lithium enolate of (?)-(1R,4R,5S,6R)-6-exo-[(tert-butyl)dimethylsilyloxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.1] heptan-2-one ((?)- 38 ; derived from (+)- 1 ) gave a 3:2 mixture of aldols (+)- 39 and (+)- 40 (mismatched pairs of a α-methyl-substituted aldehyde and (E)-enolate) whereas the reaction of (±)- 34 with (±)- 38 gave a 10:1 mixture of aldols (±)- 41 and (±)- 39 . A single aldol, (?)- 44 , was obtained to condensing (+)- 34 with the lithium enolate of (+)-(1S,4S,5S,6S)-5-exo-(benzyloxy)-1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptan-2-one ((+)- 43 ; derived from (?)-(1S,2R,4S)-2-exo-cyano-1,5-dimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl (1′S)-camphanate ((?)- 3 )). All these cross-aldolisations are highly exo-face selective for the bicyclic ketones. The best stereochemical matching is obtained when the lithium enolates and α-methyl-substituted aldehydes can realize a ‘chelated transition state’ that obeys the Cram and Felkin-Anh models (steric effects). Polypropionate fragments containing eleven contiguous stereogenic centres and tertiary-alcohol moieties are thus prepared with high stereoselectivity in a convergent fashion. The chiral auxiliaries ((1R)- and (1S)-camphanic acid) are recovered at the beginning of the syntheses.