Synthesis of (-)-calicoferol B

The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I, prepared in enantiomerically pure form, was converted into the CD ring chiron II. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of III. The first total synthesis of (-)-calicoferol B (1) is described. The cyclozirconation product 8, prepared in enantiomerically pure form, was converted into the CD ring chiron 6. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of 1.     

Total synthesis of (-)-histrionicotoxin 285A and (-)-perhydrohistrionicotoxin

Starting from commercially available ( S)-glycidol, and via a common intermediate, the total synthesis of (-)-histrionicotoxin 285A and (-)-perhydrohistrionicotoxin has been achieved. Key to this synthesis was the efficient construction of a six-membered, chiral, cyclic nitrone.     

Total synthesis of (+/-)-5,14-bis-epi-spirovibsanin A

The total synthesis of (+/-)-5,14-bis-epi-spirovibsanin A was achieved in 18 steps. Physical data obtained from (+/-)-5,14-bis-epi-spirovibsanin A lends strong support to the proposed connectivity and relative stereochemistry of spirovibsanin A.     

Total synthesis of (-)-21-isopentenylpaxilline

[structure: see text] The total synthesis of (-)-21-isopentenylpaxilline (1) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (-)-5, a highly efficient union of the eastern and western fragments (-)-5 and 4, respectively, exploiting our 2-substituted indole synthesis, and a new protocol for the construction of ring C.     

Total synthesis of (-)-13-oxyingenol and its natural derivative

Ring functionalization: the total synthesis of a natural derivative of (-)-13-oxyingenol, a potent anti-HIV diterpenoid, is reported. The key steps in this synthesis include a ring-closing olefin metathesis and a Mislow-Evans-type [2,3]-sigmatropic rearrangement. This synthesis provides access to (-)-13-oxyingenol and its natural derivative in 21 steps from a synthetic intermediate previously prepared by Kigoshi and co-workers.     

Stereocontrolled synthesis of polyfunctionalized cis-decalins from 2-methoxyphenols: total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta-angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane

A four-step stereocontrolled synthesis of polyfunctionalized cis-decalins is described, involving oxidation of 2-methoxyphenol, intermolecular Diels-Alder reaction, olefination, and Cope rearrangement. Application of this efficient strategy to the total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta-angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane was accomplished from creosol and ethyl vinyl ketone via a common intermediate 21.     

Stereoselective synthesis of (-)-cephalotaxine and C-7 alkylated analogues

A total asymmetric synthesis of (-)-cephalotaxine is reported. The chemistry of alpha,beta-unsaturated gamma-lactams was used to access the 1-azaspiro[4.4]nonane skeleton in enantiomerically pure form via a stereocontrolled semipinacolic rearrangement of an alpha-hydroxyiminium ion. This spiro compound was transformed into (-)-cephalotaxine without any racemization or epimerization by following the racemic synthesis reported by Kuehne. We thus performed a total synthesis of (-)-cephalotaxine in 98.7% ee with an overall yield of 9.8% over a 16 steps sequence. This synthetic process was adaptable to the access of some alkylated analogues.     

A concise and efficient synthesis of (-)-allosamizoline

A regio- and stereocontrolled total synthesis of (-)-allosamizoline is described. The key steps for this synthesis are ring-closing metathesis to form the cyclopentene core, halocyclization to afford the oxazoline ring, and finally stereoselective alkene radical addition followed by an alkene isomerization reaction to install the hydroxymethyl group. (-)-Allosamizoline was prepared in a total of 13 steps and 22% overall yield.     

Total synthesis of an immunosuppressive glycolipid, (2S,3S,4R)-1-O- (alpha-d-galactosyl)-2- tetracosanoylamino-1,3,4-nonanetriol

[reaction: see text] A practical and efficient total synthesis of (2S,3S,4R)-1-O-(alpha-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonanetriol, OCH 1b, a potential therapeutic candidate for Th1-mediated autoimmune diseases, is described. The synthesis incorporates direct alkylation onto epoxide 5 and stereospecific halide ion catalyzed alpha-glycosidation reaction. A key intermediate 10 was obtained in only eight steps and 37% overall yield from commercially available d-arabitol 2, and the total synthesis of 1b was accomplished in 12 steps and 19% overall yield. This method will enable the synthesis of a variety of phytosphingolipids, especially that with the shorter sphingosine side chain than 1a, in a highly stereoselective manner.     

General and efficient strategy for erythrinan and homoerythrinan alkaloids: syntheses of (+/-)-3-demethoxyerythratidinone and (+/-)-erysotramidine

[reaction: see text] A general and efficient strategy to both aromatic-type and nonaromatic-type erythrinan and homoerythrinan alkaloids has been developed. This approach involves a key two-step sequence, an alkylation of a ketone with various N-substituted iodoacetamides followed by a N-acyliminium ion promoted intramolecular cyclization, and represents one of the shortest routes to erythrinan and homoerythrinan alkaloids. As the application, the formal total synthesis of (+/-)-3-demethoxyerythratidinone and the total synthesis of (+/-)-erysotramidine have been achieved, respectively.     

Total synthesis of (-)-8-O-methyltetrangomycin (MM 47755)

A stereoselective total synthesis of the natural antibiotic (-)-8-O-methyltetrangomycin 1 is reported. The essential steps for this convergent synthesis are the transformation of a geraniol epoxide into a chiral octadiyne derivative, which was converted into a triyne. The cobalt-mediated [2+2+2] cycloaddition of the triyne led to a benz[a]anthracene system, which was oxidized with Ag(Py)(2)MnO(4) to a benz[a]anthraquinone. Deprotection with aqueous HF in acetonitrile and photooxidation afforded the desired product (-)-1. [reaction: see text]     

Total synthesis of the tricyclic marine alkaloids (-)-lepadiformine, (+)-cylindricine c, and (-)-fasicularin via a common intermediate formed by formic acid-induced intramolecular conjugate azaspirocyclization

A very short and efficient enantioselective total synthesis of the tricyclic marine alkaloids (-)-lepadiformine (3), (+)-cylindricine C (1c), and (-)-fasicularin (4) has been developed utilizing the formyloxy 1-azaspiro[4.5]decane 5 as a common intermediate. The key strategic element for the synthesis was the formic acid-induced intramolecular conjugate azaspirocyclization, which proved to be a highly efficient and stereoselective way to rapid construction of the 1-azaspirocyclic substructure of these natural products in a single operation. Thus, the common intermediate 5, synthesized in two steps with 70% overall yield starting from the known (S)-N-Boc-2-pyrrolidinone 7 via the conjugate spirocyclization using an acyclic ketoamide 6, was utilized for the concise and stereoselective total synthesis of (-)-lepadiformine (3), which was accomplished in seven steps with 45% overall yield from 5 (31% yield from 7). The developed strategy based on the conjugate spirocyclization was also applied to the stereoselective total synthesis of (+)-cylindricine C (1c), which was achieved in 10 steps from 5 in 18% overall yield (12% yield from 7). Further application of this approach using 5 led to the synthesis of (-)-fasicularin (4), wherein an extremely efficient method for the introduction of the thiocyanato group via an aziridinium intermediate at the last step was developed. Thus, the highly efficient first enantioselective total synthesis of (-)-fasicularin was accomplished in nine steps with an overall yield of 41% from 5 (28% yield from 7).     

Regiospecific, enantiospecific total synthesis of the 12-alkoxy-substituted indole alkaloids, (+)-12-methoxy-Na-methylvellosimine, (+)-12-methoxyaffinisine, and (-)-fuchsiaefoline

[reaction: see text] The enantiospecific synthesis of 7-methoxy-d-tryptophan was completed by combination of the Larock heteroannulation process with a Sch?llkopf-based chiral auxiliary in good yield. This ester was then employed in the first total synthesis of (+)-12-methoxy-Na-methylvellosimine, (+)-12-methoxyaffinisine, and (-)-fuchsiaefoline in regiospecific, stereospecific fashion in excellent overall yield. The asymmetric Pictet-Spengler reaction and enolate-driven palladium-catalyzed cross coupling processes served as key steps.     

Enantioselective syntheses of (-)- and (+)-monomorine I

A concise enantioselective total synthesis of unnatural (-)-monomorine I has been achieved starting from lactam 2 in 54% overall yield. Natural (+)-monomorine I was also synthesized.     

Total synthesis of (+/-)-spiroxin C

[reaction: see text] The first total synthesis of a marine-derived potent antitumor antibiotic, (+/-)-spiroxin C, was achieved via a TBAF-activated Suzuki-Miyaura cross-coupling reaction as a key step, which was also shown to be useful for the synthesis of sterically hindered binaphthyl derivatives.     

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.     

An improved total synthesis of (+)-macroline and alstonerine as well as the formal total synthesis of (-)-talcarpine and (-)-anhydromacrosalhine-methine

An intramolecular Pd-catalyzed alpha-vinylation process is described. This cyclization has been employed for the enantiospecific total synthesis of gram quantities of both (+)-macroline 3 and the macroline equivalent 4. This sequence is compared to the enolate-driven cross-coupling process. The intermediate 4 was also converted into (-)-alstonerine 1 via modification of an intramolecular Tsuji-Wacker oxidation. This sequence resulted in an improved total synthesis of (-)-talcarpine 5 and (-)-anhydromacrosalhine-methine 6 as well.     

A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide and approaches to the syntheses of (+/-)-6-epi-, (+/-)-15-epi-, and (+/-)-6,15-bisepidysidiolide

A formal total synthesis of the sesterterpenoid (+/-)-dysidiolide (1), a structurally novel sponge metabolite that inhibits the cdc25A protein phosphatase, and approaches to the syntheses of (+/-)-15-epi- (34), (+/-)-6-epi- (36), and (+/-)-6, 15-bisepidysidiolide (39) are described.     

Enantiospecific Synthesis of 5-Methoxy-D(+)- OR L(-) Tryptophan

A method for the enantiospecific synthesis of 5-methoxy-D(+)-tryptophan 8 or the L(-)-optical antipode is described. This procedure can be scaled up and performed without the need for extensive chromatographic separations. It provides for the first time the synthesis of the optically pure 5-methoxy-D(+) or L(-)-tryptophans required for alkaloid total synthesis.     

Total synthesis and biological evaluation of (-)-9-deoxy-englerin A

An effective total synthesis of (-)-9-deoxy-englerin (4), an analogue of the natural guaiane sesquiterpene englerin A (1), has been achieved. The synthesis features a transannular epoxide opening to construct the 5,7-fused ring system followed by transannular ether formation with mercury(II) trifluoroacetate.