Synthesis of Elemane Bis-Lactones from Santonin – Synthesis of the Reported Structure ofseco-Isoerivanin Pseudo Acid and Formal Synthesis of (+)-8-Deoxyvernolepin

Stereoselective Synthesis of (+)-11 β H ,13-Dihydroestafiatin, (+)-11 β H ,13-Dihydroludartin, (−)-Compressanolide, and (−)-11 β H ,13-Dihydromicheliolide from Santonin

“…3,4,10 As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin (1) through photochemical rearrangement. [11][12][13][14] In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. [15][16][17] With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin (4), (+)-dihydroludartin ( 5), (-)-compressanolide (6), and (-)-dihydromicheliolide (7).…”

“…Santonin ( 1 ), a commercially available natural eudesmanolide that possesses a trans -6α,12-lactone moiety, constitutes a good starting material for the syntheses of guaianolides. , In these syntheses the transformation of eudesmane to guaiane skeleton has been carried out through photochemical rearrangement of the cross-conjugated dienone system of santonin ,, or solvolytic rearrangement of 1β-tosyloxy or 1β-mesyloxy trans -decalin derivatives prepared from 1 . ,, As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin ( 1 ) through photochemical rearrangement. − In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. − With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12-guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin ( 4 ), (+)-dihydroludartin ( 5 ), (−)-compressanolide ( 6 ), and (−)-dihydromicheliolide ( 7 ).

…”

Stereoselective Synthesis of (+)-11 β H ,13-Dihydroestafiatin, (+)-11 β H ,13-Dihydroludartin, (−)-Compressanolide, and (−)-11 β H ,13-Dihydromicheliolide from Santonin

“…3,4,10 As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin (1) through photochemical rearrangement. [11][12][13][14] In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. [15][16][17] With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin (4), (+)-dihydroludartin ( 5), (-)-compressanolide (6), and (-)-dihydromicheliolide (7).…”

“…Santonin ( 1 ), a commercially available natural eudesmanolide that possesses a trans -6α,12-lactone moiety, constitutes a good starting material for the syntheses of guaianolides. , In these syntheses the transformation of eudesmane to guaiane skeleton has been carried out through photochemical rearrangement of the cross-conjugated dienone system of santonin ,, or solvolytic rearrangement of 1β-tosyloxy or 1β-mesyloxy trans -decalin derivatives prepared from 1 . ,, As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin ( 1 ) through photochemical rearrangement. − In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. − With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12-guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin ( 4 ), (+)-dihydroludartin ( 5 ), (−)-compressanolide ( 6 ), and (−)-dihydromicheliolide ( 7 ).

…”

Synthesis of Plagiochiline N from Santonin

“…Although some methods for the construction of such a system can be found in the literature, they either start from materials not easily available or do not give the proper stereochemistry and functionality for the synthesis of plagiochiline N ( 3 ). For this reason we envisaged a synthesis of plagiochiline N ( 3 ) starting from O -acetylisophotosantonin ( 2 ), a compound with a bicyclo[5,3,0]decane skeleton that can be easily obtained by photochemical rearrangement of santonin ( 1 ) in a well-known procedure. , Further transformation of compound 2 into plagiochiline N ( 3 ) should involve the substitution of the lactone moiety by a gem -dimethylcyclopropane ring between C 6 −C 7 by one hand, and transformation of the cyclopentane ring into a dihydropyran by the other. For the first part, since the stereochemistry of C 7 in compound 2 was the opposite of that of plagiochiline N ( 3 ), it became necessary to remove the C 11 −C 13 carbon fragment and to introduce the gem -dimethylcyclopropane ring later by cyclopropanation of a synthetic intermediate having a C 6 −C 7 double bond.…”

“…Procedure B. A solution of compound 6a (370 mg, 1.21 mmol), obtained upon reduction of O -acetylisophotosantonin ( 2 ) with NaTeH (92% yield),8a in EtOH (4.9 mL) was treated with 5% aqueous KOH (66 mL) overnight. After this time, 18% aqueous HCl was added until a pH of 2 was reached, and the mixture was stirred for 30 min.…”

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-β-rotunol and All Diastereomers of 6,11-Spirovetivadiene

“…In the past decade, our group has carried out intense research on the synthesis of sesquiterpenes using santonin ( 6 ) as starting material in most of the cases . The availability and functionality of this compound makes it a suitable starting material for the synthesis of other sesquiterpenes, especially eudesmanes, guaianes, and elemanes .…”

Stereoselective Synthesis of (+)-11 β H ,13-Dihydroestafiatin, (+)-11 β H ,13-Dihydroludartin, (−)-Compressanolide, and (−)-11 β H ,13-Dihydromicheliolide from Santonin

“…3,4,10 As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin (1) through photochemical rearrangement. [11][12][13][14] In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. [15][16][17] With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin (4), (+)-dihydroludartin ( 5), (-)-compressanolide (6), and (-)-dihydromicheliolide (7).…”

“…Santonin ( 1 ), a commercially available natural eudesmanolide that possesses a trans -6α,12-lactone moiety, constitutes a good starting material for the syntheses of guaianolides. , In these syntheses the transformation of eudesmane to guaiane skeleton has been carried out through photochemical rearrangement of the cross-conjugated dienone system of santonin ,, or solvolytic rearrangement of 1β-tosyloxy or 1β-mesyloxy trans -decalin derivatives prepared from 1 . ,, As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin ( 1 ) through photochemical rearrangement. − In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. − With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12-guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin ( 4 ), (+)-dihydroludartin ( 5 ), (−)-compressanolide ( 6 ), and (−)-dihydromicheliolide ( 7 ).

…”

Synthesis of Plagiochiline N from Santonin

“…Although some methods for the construction of such a system can be found in the literature, they either start from materials not easily available or do not give the proper stereochemistry and functionality for the synthesis of plagiochiline N ( 3 ). For this reason we envisaged a synthesis of plagiochiline N ( 3 ) starting from O -acetylisophotosantonin ( 2 ), a compound with a bicyclo[5,3,0]decane skeleton that can be easily obtained by photochemical rearrangement of santonin ( 1 ) in a well-known procedure. , Further transformation of compound 2 into plagiochiline N ( 3 ) should involve the substitution of the lactone moiety by a gem -dimethylcyclopropane ring between C 6 −C 7 by one hand, and transformation of the cyclopentane ring into a dihydropyran by the other. For the first part, since the stereochemistry of C 7 in compound 2 was the opposite of that of plagiochiline N ( 3 ), it became necessary to remove the C 11 −C 13 carbon fragment and to introduce the gem -dimethylcyclopropane ring later by cyclopropanation of a synthetic intermediate having a C 6 −C 7 double bond.…”

“…Procedure B. A solution of compound 6a (370 mg, 1.21 mmol), obtained upon reduction of O -acetylisophotosantonin ( 2 ) with NaTeH (92% yield),8a in EtOH (4.9 mL) was treated with 5% aqueous KOH (66 mL) overnight. After this time, 18% aqueous HCl was added until a pH of 2 was reached, and the mixture was stirred for 30 min.…”

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-β-rotunol and All Diastereomers of 6,11-Spirovetivadiene

“…In the past decade, our group has carried out intense research on the synthesis of sesquiterpenes using santonin ( 6 ) as starting material in most of the cases . The availability and functionality of this compound makes it a suitable starting material for the synthesis of other sesquiterpenes, especially eudesmanes, guaianes, and elemanes .…”

Stereoselective Synthesis of (+)-11 β H ,13-Dihydroestafiatin, (+)-11 β H ,13-Dihydroludartin, (−)-Compressanolide, and (−)-11 β H ,13-Dihydromicheliolide from Santonin

“…3,4,10 As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin (1) through photochemical rearrangement. [11][12][13][14] In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. [15][16][17] With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin (4), (+)-dihydroludartin ( 5), (-)-compressanolide (6), and (-)-dihydromicheliolide (7).…”

“…Santonin ( 1 ), a commercially available natural eudesmanolide that possesses a trans -6α,12-lactone moiety, constitutes a good starting material for the syntheses of guaianolides. , In these syntheses the transformation of eudesmane to guaiane skeleton has been carried out through photochemical rearrangement of the cross-conjugated dienone system of santonin ,, or solvolytic rearrangement of 1β-tosyloxy or 1β-mesyloxy trans -decalin derivatives prepared from 1 . ,, As a continuation of our research program on the synthesis of biologically active sesquiterpenoids, we have carried out the synthesis of several natural guaianolides from santonin ( 1 ) through photochemical rearrangement. − In a previous paper 11 we reported a synthesis of guaianolide 2 (isocostus lactone) and 3 from 1 that improved significantly on earlier reports. − With these compounds as intermediates, a straightforward approach to the synthesis of other 6,12-guaianolides was possible and we report herein the synthesis of (+)-dihydroestafiatin ( 4 ), (+)-dihydroludartin ( 5 ), (−)-compressanolide ( 6 ), and (−)-dihydromicheliolide ( 7 ).

…”

Synthesis of Plagiochiline N from Santonin

“…Although some methods for the construction of such a system can be found in the literature, they either start from materials not easily available or do not give the proper stereochemistry and functionality for the synthesis of plagiochiline N ( 3 ). For this reason we envisaged a synthesis of plagiochiline N ( 3 ) starting from O -acetylisophotosantonin ( 2 ), a compound with a bicyclo[5,3,0]decane skeleton that can be easily obtained by photochemical rearrangement of santonin ( 1 ) in a well-known procedure. , Further transformation of compound 2 into plagiochiline N ( 3 ) should involve the substitution of the lactone moiety by a gem -dimethylcyclopropane ring between C 6 −C 7 by one hand, and transformation of the cyclopentane ring into a dihydropyran by the other. For the first part, since the stereochemistry of C 7 in compound 2 was the opposite of that of plagiochiline N ( 3 ), it became necessary to remove the C 11 −C 13 carbon fragment and to introduce the gem -dimethylcyclopropane ring later by cyclopropanation of a synthetic intermediate having a C 6 −C 7 double bond.…”

“…Procedure B. A solution of compound 6a (370 mg, 1.21 mmol), obtained upon reduction of O -acetylisophotosantonin ( 2 ) with NaTeH (92% yield),8a in EtOH (4.9 mL) was treated with 5% aqueous KOH (66 mL) overnight. After this time, 18% aqueous HCl was added until a pH of 2 was reached, and the mixture was stirred for 30 min.…”

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-β-rotunol and All Diastereomers of 6,11-Spirovetivadiene

“…In the past decade, our group has carried out intense research on the synthesis of sesquiterpenes using santonin ( 6 ) as starting material in most of the cases . The availability and functionality of this compound makes it a suitable starting material for the synthesis of other sesquiterpenes, especially eudesmanes, guaianes, and elemanes .…”