Stereoselective total synthesis of (−)-decarestrictine D from l-malic acid

A convergent stereoselective total synthesis of (−)-decarestrictine D from l-malic acid is reported.     

New succinamic acids, -γ-lactones, and -succinimides from (3-perfluoroalkyl-2-iodoalkyl)succinic acid anhydrides and amines : Highly surface active amphiphiles

The (3-perfluoroalkyl-2-iodoalkyl)succinic anhydrides (4 and 5) react with primary (RNH₂) and secondary amines (RYNH) to yield (3-F-alkyl-2-iodoalkyl)succinamic acids. A second mole of RYNH gives the conjugate bases, 7a and 7b, as two position isomers. Only the C-1 isomer 7a can cyclize to a γ-lactone, while the carboxylate ion intramolecularly displaces iodide ion from CHI as RYNH₂⁺I⁻. Simultaneously, the nucleophilic carboxylate at C-4 in the unreacted isomer 7b attacks the CONHYR group at C-1 to displace the amine and revert to the anhydride 4. Then Step (1) is repeated until all of 7a and 7b are consumed. Though a weak base, COO⁻ is an effective nucleophile in the coiled conformation of 7a or 7b. In the next step, the CH₂(CO)NHR group of the γ-lactone, with an N-attack at the carbonyl rearranges to an N-alkyl (3-F-alkyl-2-hydroxypropyl)succinimide. As above, the lactone opens its ring under stereoelectronic control (with proper alignment of lone pairs on the two O atoms) and forms a new succinimide ring. These reactions occur, successively, in an aprotic, low polarity solvent under mild conditions. Elimination of HI from 4 or 5, or the iodopropylsuccinamic acid, does not occur. Diamines, e.g. (CH₃)₂N(CH₂)₃NH₂ (23) or (CH₃)₂N(CH₂)₃NH(CH₃) (27), reacting with 1 mol of 4 or 5, yield the zwitterionic salt., which inter alia, cyclizes smoothly to the γ-lactone HI salt. The lactone.HI salt from 23, as above, rearranges to the N-(dimethylammonium)propyl (3-F-alkyl-2-hydroxypropyl)succinimide iodide, while the lactone salt 33HI from diamine 27, like that from diethylamine, does not rearrange. Diamine 23, reacting with the t-butyl half ester, R_FCH₂CHICH₂CH(CO₂H)CH₂CO₂C(CH₃)₃, displaces t-butyl alcohol to yield the zwitterionic salt and γ-lactone HI salt, but not the succinimide. Radical addition of R_FI to N-butyl prop-2-enylsuccinimide (100 °C; no solvent) provides the desired adduct in high yield. By contrast, N-(3-dimethylamino)propyl (3-F-alkyl-2-iodopropyl)succinimide (25), loses HI intramolecularly to the basic (CH₃)₂N group; the concentration of 25 is 10 times greater than amines in reactions above. The R_F-surfactants (nonionic, zwitterionic, anionic, and cationic salts) of this work have an oriented F-alkyl segmented tail and a fairly complex polar head; and as a group, they lower the surface tension (γ_a) of water to 15-17 mN m⁻¹ at 1.5-1.7 mM concentration.     

Stereoselective Total Synthesis of Botryolide E and Ophiocerin C

A highly stereoselective approach to the total synthesis of the γ‐lactone derivative botryolide E and tetrahydropyran derivative ophiocerin C via a common polyketide precursor by means of Prins cyclization and MacMillan α‐aminoxylation sequence is described. The method can conveniently be utilized for the preparation of further related γ‐lactone and tetrahydropyran derivatives.     

Enantioselective synthesis of decarestrictine J

An efficient total synthesis of decarestrictine J has been achieved using ring-closing metathesis and Yamaguchi esterification as key steps. The stereogenic centres were generated by means of iterative hydrolytic kinetic resolution (HKR) of racemic epoxides.     

Stereoselective synthesis of the cytotoxic macrolide aspergillide B

A total, stereoselective synthesis of the cytotoxic macrolide aspergillide B has been performed. A cross metathesis and a C-glycosidation via a Mukaiyama-type aldol reaction were key features of the synthesis. The macrocyclic lactone ring was created by means of the Yamaguchi procedure.     

Total synthesis of Z-isomer of phomolide B

We have achieved the synthesis of Z-isomer of phomolide B during our investigation toward the effect of protecting group on the outcome of ring-closing metathesis reaction. The other key reactions involved are cis-selective partial hydrogenation, Sharpless asymmetric epoxidation, Yamaguchi esterification, and following 12 longest linear sequence with 18.5% overall yield starting from a known intermediate 20.     

Alternative total synthesis of (+)-aspicilin

The total synthesis of an 18-membered polyhydroxylated macrolide (+)-Aspicilin was accomplished starting from commercially available enantiopure propylene oxide and D-(+)-gluconolactone by asymmetric synthetic approach. The key reactions involved are Witttig reaction, Sharpless asymmetric dihydroxylation, and Yamaguchi macrolactonization.     

First stereoselective total synthesis of helicascolides A and C

The first total synthesis of helicascolides A and C is reported via acid catalyzed acetonide deprotection followed by intramolecular lactonization in one-pot as the key step.     

A Stereoselective Total Synthesis of Verbalactone

A stereoselective total synthesis of verbalactone has been achieved starting from commercially available hexanal. The sequence involves Maruoka allylation, diastereoselective iodine‐induced electrophillic cyclization, ring opening of epoxide, and Yamaguchi macrolactonization as the key steps.     

First stereoselective total synthesis of decarestrictine O via RCM protocol

A convergent first stereoselective total synthesis of decarestrictine O via RCM protocol starting from 1,3-propanediol and propylene oxide is reported.