The first regiospecific, enantiospecific total synthesis of 6-oxoalstophylline and an improved total synthesis of alstonerine and alstophylline as well as the bisindole alkaloid macralstonine

A Wacker sequence has been modified to rapidly generate ring E of (-)-alstonerine, (+)-6-oxoalstophylline, and (-)-alstophylline via a domino process. This one-pot sequence provides facile entry into the dihydropyranyl enone unit of many Alstonia alkaloids. [structure: see text]     

Enantiospecific total synthesis of the sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction

The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N(a)-H, N(b)-benzyl tetracyclic ketone 15a via the asymmetric Pictet-Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an N(b)-benzyl/N(b)-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/sarpagine related indole alkaloids and their antipodes for biological screening.     

Convergency and divergency as strategic elements in total synthesis: the total synthesis of (-)-drupacine and the formal total synthesis of (+/-)-cephalotaxine, (-)-cephalotaxine, and (+)-cephalotaxine

A concise route toward the syntheses of (-)-drupacine and (+)- and (-)-cephalotaxine has been developed. The syntheses rely on Pd(II)-catalyzed aerobic oxidative heterocyclization chemistry, which was employed to rapidly construct an important spirocyclic amine intermediate. A dynamic beta-elimination/conjugate addition process was strategically applied to complete the first asymmetric total synthesis of (-)-drupacine.     

An expedient total synthesis of (-)-dactylolide and formal synthesis of (-)-zampanolide

[reaction: see text] A highly convergent and efficient total synthesis of (-)-dactylolide and formal synthesis of (-)-zampanolide is reported.     

Enantiospecific total synthesis of (-)-(E)16-epiaffinisine, (+)-(E)16-epinormacusine B,and (+)-dehydro-16-epiaffinisine as well as the stereocontrolled total synthesis of alkaloid G

An efficient strategy is described for the total synthesis of the sarpagine-related indole alkaloids (-)-(E)16-epiaffinisine (1), (+)-(E)16-epinormacusine B (2), and (+)-dehydro-16-epiaffinisine (4). A key step employed the chemospecific and regiospecific hydroboration/oxidation at C(16)-C(17); this method has also resulted in the synthesis of (+)-dehydro-16-epinormacusine B (5). The oxy-anion Cope rearrangement followed by protonation of the enolate that resulted under conditions of kinetic control has been employed to generate the key asymmetric centers at C(15), C(16), and C(20) in alkaloid G (7) in a highly stereocontrolled fashion (>43:1). Conditions that favor control of the sarpagine stereochemistry at C(16) vs the epimeric ajmaline configuration at the same stereocenter have been determined. The formation of the required cyclic ether in 4, 5, and 7 was realized with complete control from the top face on treatment of the corresponding alcohols with DDQ/THF or DDQ/aq THF in excellent yields.     

A (formal) total synthesis of (+) - strigol,the witchweed germination factor

A synthetic route to (+)-1 commencing from (S)-malic acid and 20 is reported. Key steps are the coupling of 20 and 15 to give 21, an intramolecular Wittig reaction (25-→27), and an oxidative cyclization (28-→1).     

Chemoenzymatic formal synthesis of (-)- and (+)-epibatidine

The cis-dihydrocatechol, derived from enzymatic cis-dihydroxylation of bromobenzene using the microorganism Pseudomonas putida UV4, was converted into (-)-epibatidine in eleven steps with complete stereocontrol. In addition, an unprecedented palladium-catalysed disproportionation reaction gave the (+)-enantiomer of an advanced key intermediate employed in a previous synthesis of epibatidine.     

Enantiospecific, stereospecific total synthesis of (+)-majvinine, (+)-10-methoxyaffinisine, and (+)-N(a)-methylsarpagine as well as the total synthesis of the Alstonia bisindole macralstonidine

[structure: see text] The enantiospecific stereospecific total synthesis of majvinine 1a, 10-methoxyaffinisine 1b, and N(a)-methylsarpagine 1c are reported; this method has also resulted in the total synthesis of the Alstonia bisindole macralstonidine 2.     

Stereoselective formal total synthesis of (+)-methynolide

A highly stereoselective and convergent formal total synthesis of (+)-methynolide is described. The salient features of this synthesis have been the construction of the C1-C7 and C8-C11fragments via a desymmetrization approach, Sharpless asymmetric epoxidation of an allyl alcohol, respectively, and linkage of both the fragments by Nozaki-Hiyama-Kishi reaction.     

Enantioselective total synthesis of (-)- and (+)-petrosin

The enantioselective total synthesis of (-)- and (+)-petrosin is described. The union of two key segments was executed by Suzuki-Miyaura coupling. The quinolizidine rings were stereoselectively constructed via a diastereoselective Mannich reaction and an aza-Michael reaction. The 16-membered ring was constructed by ring-closing metathesis with the second-generation Grubbs catalyst.     

Diastereoselective total synthesis of (+)-13-stemarene by fourth generation methods: a formal total synthesis of (+)-18-deoxystemarin

The problem of constructing diastereoselectively the C/D ring system of stemarane diterpenes from a bicyclo[2.2.2]octane intermediate was solved resulting in very simple synthesis of (+)-13-stemarene 1. The obtaining of the latter represents also a formal synthesis of (+)-18-deoxystemarin 2. In the key step, the epimeric mixture 10, dissolved in toluene, was converted by the action of TsOH into (+)-stemar-13-en-15-one 28.     

A formal total synthesis of (-)-cephalotaxine.

A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound.     

Asymmetric total synthesis and formal total synthesis of the antitumor sesquiterpenoid (+)-eremantholide A

[structure: see text]. A new asymmetric total synthesis of (+)-eremantholide A is reported in which a Hoveyda-Grubbs ring-closing metathesis (RCM) reaction is used to assemble the nine-membered oxonin ring, and an enolate alkylation between the 3(2H)-furanone 2 and O-triflate 3 is exploited for C(9)-C(10) bond construction. An Evans asymmetric aldol reaction and a Sharpless asymmetric epoxidation served to stereoselectively install the C(6), C(7), and C(8) stereocenters of the target structure.     

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H has been achieved. Key step involved construction of all-carbon quaternary carbon by palladium-catalyzed conjugate addition of arylboronic acid to 3-methyl cyclohexenone. Furthermore, a new approach to build [6-5-6] tricyclic backbone via formyl introduction and subsequent aldol-type condensation was also explored.     

First total synthesis of (-)- and (+)-6-O-desmethylantofine

The first total synthesis of (-)-6-O-desmethylantofine (A) and its unnatural enantiomer (+)-6-O-desmethylantofine (B) is described. The synthetic route is efficient and practical with easily available glutamic acid dimethyl ester hydrochloride as the chiral material under mild conditions.     

The enantiospecific,stereospecific total synthesis of the ring-A oxygenated sarpagine indole alkaloids (+)-majvinine, (+)-10-methoxyaffinisine,and (+)-N(a)-methylsarpagine,as well as the total synthesis of the alstonia bisindole alkaloid macralstonidine

The first stereospecific, enantiospecific total synthesis of the ring-A oxygenated sarpagine indole alkaloids (+)-N(a)-methylsarpagine (8), (+)-majvinine (14), and (+)-10-methoxyaffinisine (49), as well as the first total synthesis of the Alstonia bisindole alkaloid macralstonidine (9), has been accomplished. This approach employed the Sch?llkopf chiral auxiliary for the stereospecific construction of the desired d-(+)-tryptophan unit required for the asymmetric Pictet-Spengler reaction. In addition, the strategy was doubly convergent for the enolate-mediated Pd(0) coupling process and the asymmetric Pictet-Spengler reaction can be employed to synthesize both macroline (2) and N(a)-methylsarpagine (8), the coupling of which provides macralstonidine (9). This approach to ring-A substituted alkoxyindole alkaloids should find wide application for the synthesis of other alkaloids for it is stereospecific and either enantiomer can be prepared with ease.     

An enantioselective formal synthesis of （-）-thujopsene

Dihydromayurone （3）, a key intermediate to synthesize （-）-thujopsene （1）, was efficient enantiocontrolled synthesized from （＋）-dihydrocarvone through 9 steps in an overall yield of 19.3%. The key step was the Simmons-Smith reaction.     

An enantioselective formal synthesis of (-)-thujopsene

Dihydromayurone (3), a key intermediate to synthesize (-)-thujopsene (1), was efficient enantiocontrolled synthesized from ( )-dihydrocarvone through 9 steps in an overall yield of 19.3%. The key step was the Simmons-Smith reaction.     

Novel sparteine-mediated enantio-dichotomic formal synthesis of R-(-)- and S-(+)-curcuphenol

High and opposite enantiodiscriminations were observed between tertiary amides and secondary amides in the sparteine-mediated lateral metalation-allylation of 2-ethyl-m-toluamide derivatives (2a, 2e). The results described above have been applied for the formal synthesis of both enantiomers of curcuphenol. The brief mechanistic studies suggested that stereoinformation was introduced after the deprotonation step.