Synthesis of (-)-ambrox from ℓ-abietic acid

Synthesis of (-)-ambrox 1 has been completed stereoselectively starting from ℓ-abietic acid 2.     

First Total Synthesis of(±)-Puyanin and(±)-4'-Omethylbonannione

A facile approach for the first total synthesis of two naturally occurring geranylated flavonoids, (±)‐puyanin ( 1 ) and (±)‐4′‐O‐methylbonannione ( 2 ) has been obtained with total yields of 27% and 17.8%, respectively. The key steps were regioselective cyclization of geranylated trihydroxychalcone and regioselective geranylation of 2,4,6‐trihydroxyacetophenone.     

Synthesis of (±)-4-Demtthoxy-7 11-Dideoxydaungmy-Cinone

Our continued interest in the total synthesis of natural and unnatural antitumor anthracyclines¹ especially the aglycones such as daunomycinone (1)² and 4-demethoxydaunomycinone (2),³ 11-deoxydaunomycinone(3)⁴ and 4-demethoxy-11-deoxydau-nomycinone (4)⁵ led us to investigate various methods for obtaining these products. Recently we have reported the synthesis of 4-demethoxy-7, 11-dideoxydaunomycinone (5) from 5-methoxy-1-tetralone. Now we wish to report the synthesis of 5 starting from 5-methoxy-1-tetralone (9) which was prepared from 1,6-dimethoxy-naphthalene(8). Umezawa⁷ et al. have reported the total synthesis of 4-demethoxy-ll-deoxydaunomycin(6) and 4-demethoxy-11-deoxy-adriamycin (7) from 5-methoxy-2-tetralone.     

Synthesis of (±)-7-hydroxylycopodine

A seven-step synthesis of (±)-7-hydroxylycopodine that proceeds in 5% overall yield has been achieved. The key step is a Prins reaction in 60% sulfuric acid that gave the key tricyclic intermediate with complete control of the ring fusion stereochemistry. A one-pot procedure orthogonally protected the primary alcohol as an acetate and the tertiary alcohol as a methylthiomethyl ether. The resulting product was converted to 7-hydroxydehydrolycopodine by heating with KO-t-Bu and benzophenone in benzene followed by acidic workup. During unsuccessful attempts to make optically pure starting material, we observed the selective Pt-catalyzed hydrogenation of the 5-phenyl group of a 4,5-diphenyloxazolidine under acidic conditions and the Pt-catalyzed isomerization of the oxazolidine to an amide under neutral conditions. In attempts to hydroxylate the starting material so that we could adapt this synthesis to the preparation of (±)-7,8-dihydroxylycopodine (sauroine) we observed the novel oxidation of a bicyclic vinylogous amide to a keto pyridine with Mn(OAc)(3) and to an amino phenol with KHMDS and oxygen.     

Synthesis of (±)-7-hydroxylycopodine

A six step synthesis of (±)-7-hydroxylycopodine has been achieved in 5% overall yield. In the key step, a Prins cyclization of a bicyclic keto alkyne in 60% H(2)SO(4) forms a tricyclic dihydroxy amino ketone.     

Synthesis of (±)-zearalenone

The aliphatic portion of (±)-zearalenone has been synthesised by a new simple route starting from 2,3-dihydropyran and 2-acetyl-γ-butyrolactone by employing dithiane for C-C bond formation. The final condensation of this segment with the aromatic part and subseqnet transformations led to (±)-zearalenone.     

Synthesis of (±) Combretastatin

Combretastatin (1) is a new plant product isolated recently by Pettit et al ¹. from the South African tree, Combretum caffrum that possesses central nervous system antineoplastic activity and is being evaluated against several of National Cancer Institute's key evaluation systems. The structure of 1 was established on the basis of its spectral properties and confirmed by X-ray analysis. However, the absolute configuration and the synthesis of 1 have not been reported so far. As combretastatin is present in the plant in only 0.0008% and the isolation technique is much tedious, there is an urgent need for the synthesis of 1 for further evaluation of its activity. This prompted us t o report the first synthesis of (±)1.     

Synthesis of (±)-Altaicadispirolactone

The first synthesis of (±) Altaicadisporolactane 1 is described starting from succinic anhydride.     

Synthesis of (±)-Bimatoprost

A general synthetic approach has been developed for the synthesis of a key intermediate (6) that can be elaborated into several ophthalmic prostaglandins and their derivatives. Using these strategy, we have obtained (±)-bimatoprost (1) and its analog, (±)-homobimatoprost (5).     

Synthesis of (±)-8-deisopropyladunctin B

(±)-8-Deisopropyladunctin B, the deisopropyl form of adunctin B, which was isolated from the leaves of Piper aduncum (Piperaceae) collected in Papua New Guinea, was synthesized in 0.77% overall yield in 17 steps from 5,7-dimethoxycoumarin-3-carboxylate. The key step was our original stereoconvergent skeleton transformation from 1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-one to 1,2,4a,9b-tetrahydrodibenzofuran-4-ol with dimethylsulfoxonium methylide.     

Total Synthesis of (±)- Cis -5-Hydroxycalamenene

A total synthesis of (±)-cis-5-hydroxycalamenene 1 has been achieved from tetralone 5, which in turn was prepared from 5-methoxy-α-tetralone 3. Grignard reaction of compound 5 with isopropylmagnesium chloride, followed by dehydration and aromatization, provided the substituted naphthalene 7 whose conversion to (±)-cis-5-hydroxycalamenene 1 was accomplished by demethylation, formylation, and hydrogenation.     

Total Synthesis of (±) Thaicanine

A convenient total synthesis of (±) thaicanine (5) is described from 2-benzyloxy-3,4-dimethoxyphenylethylamine (1).     

Total Synthesis of (±)Chrysotricine

Chrysotricine1wasisolatedfromtheChineseherbmedicineHedyotiSChrysotricha'anditssthectUrehasbeenestablishedasanew0-carbolinealkaloidwitha2,5-trans-substitutedtetrahydrofuranylgrouPatitsl-positionbyX-raydiffractionandspectralanalysis.PharmaceuticalstUdiesshowedpotentialantitUmoractivity.Theinterestingbiologicalactivityandthechemistryof6-carb0linesmict[JIehaveattiactedconsiderableattentioninrecentyears.InordertostUdythisstrUctUre-activityrelationshiPfurther,wewereillterestedinthedevelopmento…     

New Synthesis of (±)Shikalkin

The naturally occurring enantiomers mixture of shikonin (R-1) and alkannin (S-1) has been named shikalkin by H.Brockmann1. Shikonin was first isolated as its acetate from the roots of Lithospermum erythrorhizon (LE) which has been used for dyeing in China, Japan, and Korea from ancient times2. Alkannin was found in Alkanna tincloria(AT) and many other type of Boraginaceous roots1. Shikalkin 1 and their ester derivatives showed antitumor3, antiinflammatory4, antibacerical5, immunostimu…     

Total Synthesis of (±)-Cuauhtemone

A total synthesis of (±)-cuauhtemone (9) was achieved by utilising the isopropylidene ketone (6) which in turn was prepared from the ketone (4).     

Total Synthesis of (±)-Corymine

The first total synthesis of the hexacyclic indole alkaloid (±)-corymine is described. Starting from the readily available N-protected tryptamine, the title compound was achieved in 21 steps in 3.4 % overall yield. Key steps of the synthesis include: a) the addition of a malonate to a 3-bromooxindole to afford 3,3-disubstituted oxindole, b) the formation of a 12-membered cyclic enol ether by intramolecular O-propargylation, immediately followed by propargyl Claisen rearrangement to provide the α-allenyl ketone stereospecifically, c) DMDO oxidation to install a hydroxy group in a highly stereoselective manner, and d) the SmI₂-mediated reductive C−O bond cleavage to remove the α-keto carboxyl group.     

Synthesis of (±)-phthalascidin 622

A synthesis of functionalized phenolic α-amino-alcohols (±)-8 and (±)-16 as synthetic precursors of the catechol tetrahydroisoquinoline structure of phthalascidin 650 was disclosed. (±)-8 was prepared in 5 steps from the commercially available sesamol. Starting from 3-methyl catechol 5, 8 steps gave rise to the synthesis of phenolic α-amino-alcohol (±)-16 in 27% overall yield. This synthetic strategy involved the elaboration of fully functionalized aromatic aldehyde 13 and its transformation into a phenolic α-amino-alcohol (±)-16, through a Knoevenagel condensation, simultaneous reduction of nitroketene and ester functions, and hydrogenolysis of the benzyl protecting group. The pentacycle (±)-4 was obtained after 4 additional steps. The Pictet-Spengler cyclisation between the phenolic α-amino-alcohol (±)-16 and the N-protected α-amino-aldehyde 4 allowed to obtain (1,3′)-bis-tetrahydroisoquinoline 17 with N-methylated and N-Fmoc removed. The last step was a Swern oxidation allowing the expected intramolecular condensation.     

Synthesis of (±)-cis-Calamenene;

Hydroboration of 4 furnishes a mixture of primary alcohols 5 and 6. The stereochemistry of the crystalline half ester 7 has been established by X-ray studies. While the oxidation of 5 with Jones reagent furnishes the aldehyde 9 in low yield due to the formation of the by product 3, oxidation with Moffatt reagent furnishes the aldehyde 9 in satisfactory yields. cis-Calamenene 1 has been prepared from 9.