A Stereoselective Total Synthesis of (±)-Maritimol, (±)-2-Deoxystemodinone, (±)-Stemodinone,and (±)-Stemodin

A simple and stereoselective total synthesis of (±)-maritimol ( 2d ) and its conversion into the other title compounds (±)-( 2a ), ((±)- 2b ), and ((±)- 2c ) is described. The unique bicyclo[3.2.1]octane moiety, constituting their C/D-ring system, is stereospecifically obtained by solvolytic rearrangement of the methanesulfonate 23 .     

A Flexible Stereoselective Synthesis of the Spirosesquiterpenes (±)-β-Acorenol, (±)-β-Acoradiene, (±)-Acorenone-B and (±)-Acorenone via an Intramolecular Ene-Reaction

The racemic spirosesquiterpenes β-acorenol ( 1 ), β-acoradiene ( 2 ), acorenone-B ( 3 ) and acorenone ( 4 ) (Scheme 2) have been synthesized in a simple, flexible and highly stereoselective manner from the ester 5 . The key step (Schemes 3 and 4), an intramolecular thermal ene reaction of the 1,6-diene 6 , proceeded with 100% endo-selectivity to give the separable and interconvertible epimers 7a and 7b . Transformation of the ‘trans’-ester 7a to (±)- 1 and (±)- 2 via the enone 9 (Scheme 5) involved either a thermal retro-ene reaction 10 → 12 or, alternatively, an acid-catalysed elimination 11 → 13 + 14 followed by conversion to the 2-propanols 16 and 17 and their reduction with sodium in ammonia into 1 which was then dehydrated to 2 . The conversion of the ‘cis’-ester 7b to either 3 (Scheme 6) or 4 (Scheme 7) was accomplished by transforming firstly the carbethoxy group to an isopropyl group via 7b → 18 → 19 → 20 , oxidation of 20 to 21 , then alkylative 1,2-enone transposition 21 → 22 → 23 → 3 . By regioselective hydroboration and oxidation, the same precursor 20 gave a single ketone 25 which was subjected to the regioselective sulfenylation-alkylation-desulfenylation sequence 25 → 26 → 27 → 4 .     

Synthesis of Aristotelia-type alkaloids. Part VII. Syntheses of (±)-sorelline, (±)-serratenone,and (±)-aristotelin-19-one

The imine obtained by condensing indole-protected 2-(indol-3-yl)acetaldehyde ( 5 ) with the terpinylamine derivative (±)- 4 was cyclized in 51% yield to the 19-substituted hobartine derivative (±)- 20 upon exposure to anhydrous HCOOH. This pivotal intermediate was further elaborated into the indole alkaloids (±)-serratenone ((±)- 22 ) and (±)-sorelline ((±)- 29 ). In the course of these investigations, a novel rearrangement was uncovered; a Lewis acid-catalyzed 1,3-migration of an arylsulfonyl group from the indole N-atom into the benzene ring. The discovery that synthetic (±)-aristotelin-19-one ((±)- 34 ) has decidedly different spectroscopic properties than aristolasicone, a metabolite for which the structure has been recently proposed, led to a revision of the structure of the latter.     

Total Synthesis of (±)-3-Deoxy-7,8-dihydromorphine, (±)-4-Methoxy-N-methylmorphinan-6-one and 2,4-Dioxygenated (±)-Congeners

A total synthesis of racemic 3-deoxy-7,8-dihydromorphine ((±)- 2 ) and 4-me-thoxy-ALmethylmorphinan-6-one ((±)- 3 ) is described. The key intermediate was 2,4-dihydroxy-N-formylmorphinan-6-one (11) , obtained from 3,5-dibenzyloxy-phenylacetic acid (4) in 41.8% overall yield. Bromination of 11 , and treatment with aqueous N_aOH-solution afforded, after N-deblocking and reductive N-methylation with concomitant removal of the aromatic bounded Br-atom, the morphinanone 14. Elimination of the HO–C(2) group in 14 was accomplished by hydrogenolysis of its N-phenyltetrazolyl ether 15 , to give 3-deoxy-6,0-didehydro-7,8-dihydromorphine (16). Reduction of 16 with L-Selectride at low temperature provided (±)- 2 in high yield. The ether 15 directly afforded, under more vigorous reduction conditions, 4-hydroxy-N-methylmorphinan-6-one (17). and after O-methylation of 17 , the methyl ether (±)- 3 was obtained. A (1:l)-mixture of 4-hydroxy-2-methoxy-N-methylmor-phinan-6-one (28) and its 2-hydroxy-4-methoxy isomer 30 svere obtained by Grewe-cyclization of a mono-methoxylated aromatic precursor similar to that which afforded 11. The 2,4-dioxygenated N-methylmorphinan-6-ones 29 , 31 and 38 were also prepared and characterized.     

A Bioinspired Synthesis of (±)‐Rubrobramide, (±)‐Flavipucine,and (±)‐Isoflavipucine

A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α‐bromo‐β‐ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α,β‐epoxy‐γ‐lactam. Furthermore, the absolute configuration of naturally occurring (+)‐rubrobramide was determined by vibrational circular dichroism. (±)‐Flavipucine and (±)‐isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α‐bromo‐β‐ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)‐flavipucine, which was converted into (±)‐isoflavipucine by thermal isomerization.     

A Bioinspired Synthesis of (±)‐Rubrobramide, (±)‐Flavipucine,and (±)‐Isoflavipucine

A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α‐bromo‐β‐ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α,β‐epoxy‐γ‐lactam. Furthermore, the absolute configuration of naturally occurring (+)‐rubrobramide was determined by vibrational circular dichroism. (±)‐Flavipucine and (±)‐isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α‐bromo‐β‐ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)‐flavipucine, which was converted into (±)‐isoflavipucine by thermal isomerization.     

Spirocyclization strategy toward indole phytoalexins. The first synthesis of (±)-1-methoxyspirobrassinin, (±)-1-methoxyspirobrassinol, and (±)-1-methoxyspirobrassinol methyl ether

The first syntheses of cruciferous indole phytoalexins (±)-1-methoxyspirobrassinin, (±)-1-methoxyspirobrassinol, (±)-1-methoxyspirobrassinol methyl ether as well as a new syntheses of phytoalexins (±)-spirobrassinin and cyclobrassinin were achieved by dioxane dibromide (DDB)-mediated spirocyclization of brassinin and its 1-substituted derivatives.     

Synthesis of (±)-methylenolactocin and (±)-trans cognac lactone

The title compounds were efficeintly synthesized from 3-fuancarboxylic acid via the Birch recuction-elimination.     

Total Synthesis of (±)-Patriscabrol and (±)-Boschnialactone

A total synthesis of (±)-patriscabrol (1) and (±)-boschnialactone (2) is described. The cyclopentapyranone skeleton is assembled by means of Baeyer-Villiger oxidation of ketol 5.     

Synthesen makrocyclischer Lactone durch Ringerweiterung Herstellung von (±)-Phoracantholid I, (±)-Dihydrorecifeiolid und (±)-15-Hexadecanolid

Syntheses of Macrocyclic Lactones by Ring Enlargement Reaction Reaction. Preparation of (±)-Phoracantholide I, (±)-Dihydrorecifeiolide and (±)-15-Hexadecanolide A general procedure for the synthesis of macrocyclic lactones is described. The Michael adducts of 2-nitrocycloalkanones and acrylaldehyde were regiospecifically methylated with CH₃Ti[OCH(CH₃)₂]₃ or (CH₃)₂Ti[OCH(CH₃)₂]₂ at the aldehyde carbonyl group. Treatment of the so-formed alkohols with tetrabutylammonium fluoride gave the lactones enlarged by four ring members. This method was used to synthesize the 10-membered (±)-phoracantolide I ( 11 ), the 12-membered (±)-dihydrorecifeiolide ( 17 ), and (±)-15-hexadecanolide ( 24 ) in 52%, 26.5%, and 58.7% respectively.     

Total Synthesis of (±)-2-Pupukeanone

(±)-2-Pupukenone ( 4 ) has been synthesized, the key step being the intramolcular Diels-Alder reaction of the intermediate 13 to 14 (42%) and 15 (14%). The bromodiene 12 has been obtained from the reaction of α-isopropylidene-γ-lactone (Scheme 2) 12 with sodium phenylselenide and subsequent esterification to 9 , oxidation and thermal elimination of which furnished 10 . Reduction of 10 with diisobutylaluminimum hydride and treatment of the resulting alcohol 11 with PBr₃ led to the required bromodiene 12 . Finally, hydrogenation of the 14 on Pt(C) in CH₃OH gave a 4:1 mixture of 2-pupukeanone ( 4 ) and epi-2-pupukeanone 16 .     

(±)-4-Amino-4,5-dideoxyribose, (±)-4-amino-4-deoxyerythrose,and (±)-dihydroxyproline derivatives from N-dienyl-γ-lactams

Hetero-Diels-Alder cycloaddition of acylnitroso dienophile 4 with the N-(butadienyl)pyrrolidinone derivatives 2a , b led with complete regioselectivity to the oxazine adducts 5a , b (Scheme 1). Sequential osmylation, protection of the ensuing glycol, and reduction of the N? O bond gave the expected hemiaminals 11a , b which were characterized by their crystalline sulfite adducts 12a , b (Schemes 1 and 2). Deprotection and saponification of the latter led to aminodeoxyerythrose and to aminodeoxyribose derivatives as an equilibrium of pyrrolidinose equivalents, i.e., hemiaminals 14a , b , imines 14′a , b , and dimers 14″a , b , respectively (Scheme 3). Hydrocyanic acid addition to 11a , b led ultimately to the proline derivatives 16a , b (Scheme 2). Compound 11b proved to be an inhibitor of syncytium formation in AIDS-infected cells.     

The Total Synthesis of (±)-Camphor and (±)-Epicamphorenone from Methylcyclopentadiene

The total synthesis of (±)-carnphor and (±)-epicamphorenone from methylcyclopentadiene are described.     

Facile Synthesis of (±)‐Parahigginone Methyl Ether and (±)‐Curcuphenol

Using Grinard coupling as a key step, a facile synthetic approach to (±)‐parahigginone methyl ether 1 and (±)‐curcuphenol 2 has been achieved by five steps with 42.3% and 58.6% overall yield, respectively.     

Synthesis of Aristotelia-type alkaloids. Part V. Biomimetic synthesis of (±)-aristomakine and (±)-aristomakinine

Biomimetic syntheses of racemic aristomakinine ((±)- 3 ) and aristomakine ((±)- 4 ), an unusual indole alkaloid bearing an N-isopropyl group, are described. The key step is a Grob-type fragmentation of anti-15-aristotelinyl methanesulfonate ((±)- 2 ) to the intermediate iminium ion I which, upon subsequent hydrolysis, furnished aristomakinine ((±)- 3 ). On the other hand, the same intermediate could be reduced in situ to aristomakine ((±)- 4 ). The controversial relative configurations of the two alkaloids have been firmly established by means of NOE difference experiments.     

Vicinal Dianion of Triethyl Ethanetricarboxylate: Syntheses of (±)‐Lichesterinic Acid, (±)‐Phaseolinic Acid, (±)‐Nephromopsinic Acid, (±)‐Rocellaric Acid,and (±)‐Dihydroprotolichesterinic Acid

The vicinal dianion 2 derived from triethyl ethanetricarboxylate reacted regioselectively with aldehydes and ketones at C(β) to provide paraconic acid derivatives 5a – f in moderate to high yields as mixtures of diastereoisomers. The paraconic acid derivatives 5e and 5f were utilized as the starting materials for the syntheses of (±)‐lichesterinic acid ( 12 ), (±)‐phaseolinic acid ( 13 ), (±)‐nephromopsinic acid ( 14 ), (±)‐rocellaric acid ( 15 ), and (±)‐dihydroprotolichesterinic acid ( 16 ).     

Total Synthesis of (±)‐Eusiderin G and (±)‐Eusiderin M

(±)‐Eusiderin G and (±)‐Eusiderin M were first synthesized from pyrogallol, in which the Claisen Rearrangement was used to afford two important C₆‐C₃ units.     

Formal Syntheses of (±)-Verbenalol and (±)-Udoteatrial

A formal total synthesis of (±)-verbenalol 1 and (±)-udoteatrial 2 is described. Tie key intermediate is diiodolactone 7.