Synthetic studies toward pondaplin: total synthesis of pondaplin analogues

Syntheses of synthetic analogues of pondaplin 1 have been achieved. Final macrolide construction was accomplished using a Keck macrolactonization reaction.     

Enantiospecific total synthesis of 15-hydroxy-5-(methoxymethoxy)crinipellin-9-one

Enantiospecific total synthesis of the crinipellin mentioned in the title was accomplished. In the present synthesis cyclopentane ring in campholenaldehyde was identified as the B-ring, two intramolecular rhodium carbenoid CH insertion reactions were employed for the construction of the A and C rings, and an intramolecular Michael addition reaction was utilized for the construction of the D-ring of crinipellin.     

Total synthesis of polyamine toxin HO-416b and Agel-489 using a 2-nitrobenzenesulfonamide strategy

Total synthesis of spider toxins HO-416b (1) and Agel-489 (2) was accomplished using the 2-nitrobenzenesulfonamide (Ns) group as both a protecting and activating group. In this strategy, the C-N bonds were constructed by alkylation of sulfonamides with alkyl halides or Mitsunobu reaction with the corresponding alcohol. Beginning with monoprotection of the symmetrical diamine, the construction of the backbone from diamine 3 was efficiently accomplished in 7 steps for 14 and 9 steps for 29. Removal of the Ns group while the substrate was attached to a novel solid support enabled the efficient isolation of this highly polar compound.     

Total synthesis of mycocyclosin

The first total synthesis of mycocyclosin, a diketopiperazine natural product isolated from M. tuberculosis, is described. While direct oxidative coupling of tyrosine phenolic groups was unsuccessful, construction of the highly strained bicyclic framework was successfully accomplished through an intramolecular Miyaura-Suzuki cross-coupling to generate the biaryl linkage.     

The first total synthesis of (+/-)-arisugacin A, a potent, orally bioavailable inhibitor of acetylcholinesterase

The first convergent total synthesis of (+/-)-arisugacin A was accomplished by stereoselective construction of the arisugacin skeleton via a Knoevenagel-type reaction of an alpha,beta-unsaturated aldehyde with a 4-hydroxy 2-pyrone and stereoselective dihydroxylation followed by deoxygenation.     

Synthetic studies on maitotoxin. 3. Stereoselective synthesis of the BCDE-ring system

The stereoselective synthesis of the BCDE-ring system of maitotoxin has been accomplished through a two-directional strategy for the construction of polycyclic ether. The key reactions involve SmI 2-induced double cyclization of a beta-alkoxyacrylate and a double dihydroxylation for construction of the B- and E-rings.     

Asymmetric synthesis of valilactone

Total synthesis of (?)-valilactone, an efficient pancreatic lipase inhibitor, was accomplished with the use of Keck allylation in the key step of construction of the target carbon skeleton.     

Concise enantioselective synthesis of furocaulerpin

The first total synthesis of both enantiomers of furocaulerpin was accomplished in good yields with a high control of the stereogenic center by enzymatic resolution, a total control of the configuration of the central double bond and the construction of the dienyne moiety via a Stille cross-coupling.     

Synthetic studies of zoanthamine/norzoanthamine: biogenetic-like one-step construction of the heterocyclic aminal core (CDEFG ring) from a monocyclic precursor

Biogenetic-like one-step construction of the pentacyclic aminal core of zoanthamine/norzoanthamine alkaloids was accomplished in high yield from the suitably protected monocyclic aminohydroxy diketocarboxylic acid 7 by heating in aqueous acetic acid.     

Synthesis of the ABCD fragment of gymnocin-B

A convergent synthesis of the ABCD fragment of gymnocin-B was accomplished. The tetracyclic ether ring system was synthesized by the construction of the BC ring system via the oxiranyl anion alkylation and ring expansion reaction, followed by the formation of the five-membered A-ring via a stereoselective radical cyclization reaction of a neopentyl-type iodide.     

First total synthesis of (+/-)-taxifolial a and (+/-)-iso-caulerpenyne

The first synthesis of (+/-)-taxifolial A and iso-caulerpenyne was accomplished. The key steps in the sequence are (1) the stereoselective assembly of a vinyltin derived from butynediol and a functionalized aldehyde and (2) the construction of the dienyne moiety via a Stille cross-coupling.     

The first total synthesis of (+/-)-scopadulin, an antiviral aphidicolane diterpene

[reaction: see text] The first total synthesis of (+/-)-scopadulin was accomplished by a stereoselective construction of a quaternary carbon at C-4, conversion of the hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols, and a highly chemo- and stereoselective methylation at C-16.     

Stereocontrolled synthesis of (+)-methoxyphenylkainic acid and (+)-phenylkainic acid

The efficient total syntheses of (+)-methoxyphenylkainic acid (3) and (+)-phenylkainic acid (4) were achieved using a rhodium carbenoid-mediated intermolecular C-H insertion reaction. Complete stereoselective construction of the kainoid skeleton was accomplished by utilizing the stereochemistry at the C-4 position as a pivotal stereogenic center.     

Synthetic construction of a Le determinant via gabriel amine synthesis and the glycopolymer involving highly clustered Le residues

Synthetic construction of a Le^x determinant was accomplished via slightly modified Gabriel amine synthesis from three building blocks. Further transformations followed by polymerization of the Le^x derivative gave a glycopolymer having trisaccharidic units as pendant-type epitopes.     

Self-Assembly of Quinodimethanes through Covalent Bonds: A Novel Principle for the Synthesis of Functional Macrocycles

A multiplication of functional units was accomplished in a simple fashion by the tetramerization of a quinodimethane. This principle is demonstrated by the convergent construction of a macrocyclic molecule with 16 ferrocenes and a macrocyclic molecule with 16 dendritic units at the periphery of the molecule (see scheme). FG=functional group     

Model studies toward the synthesis of the bioactive diterpenoid, harringtonolide

In model studies towards the synthesis of harringtonolide, the construction of the tropone moiety via arene cyclopropanation was investigated. The installation of the lactone ring was accomplished by way of a Diels-Alder cycloaddition of various indenones and a-pyones. The incorporation of the key bridge methyl group and subsequent control of its stereochemistry is also outlined.     

Stereocontrolled total synthesis of (-)-eudistomin C

A stereocontrolled total synthesis of (-)-eudistomin C was accomplished in 18-step sequence with an overall yield of 7.7%. The synthesis features the diastereoselective Pictet-Spengler reaction of a tryptamine derivative and the Garner aldehyde catalyzed by Bronsted acids, and the unprecedented construction of the unusual oxathiazepine ring by intramolecular alkylation.     

Total synthesis of (+/-)-mycoepoxydiene,a novel fungal metabolite having an oxygen-bridged cyclooctadiene skeleton

[reaction: see text] The first total synthesis of (+/-)-mycoepoxydiene has been accomplished. A ring-closing olefin metathesis (RCM) approach was employed for the construction of the oxygen-bridged eight-membered bicyclic skeleton. The RCM product was converted to the target natural product featuring the oxidative rearrangement of a furfuryl alcohol introduced as the side chain and the stereoselective 1,2-reduction of a delta-keto-beta,gamma-unsaturated alpha-lactol intermediate.     

Synthesis of the fused polyether core of hemibrevetoxin B by two-directional ring-closing metathesis

The tetracyclic fused polyether core of the marine natural product hemibrevetoxin B has been prepared in an efficient manner by using a strategy in which ring-closing metathesis (RCM) reactions were employed for ring synthesis. Simultaneous construction of the A and D rings was accomplished by double two-directional RCM of a tetraene. [reaction: see text]     

Total synthesis of (±)-cycloclavine and (±)-5-epi-cycloclavine

Novel routes to the naturally occurring indole alkaloid cycloclavine and its unnatural C(5)-epimer are described. Key features include the rapid construction of the heterocyclic core segments by two Diels-Alder reactions. An indole annulation was accomplished by a late-stage intramolecular Diels-Alder furan cycloaddition, and a methylenecyclopropane dienophile was used for a stereoselective intramolecular [4 + 2] cycloaddition to give the cyclopropa[c]indoline building block present in cycloclavine.