A 3,4-disubstituted pyrrolidine ring was effectively cyclized through SmI2-mediated reductive coupling between allyl chloride and an α,β-unsaturated ester, although little has been reported about SmI2-promoted C–C bond formation of an allyl chloride with an α,β-unsaturated ester. Selection of either the 3,4-cis- or 3,4-trans-selective cyclization can be accomplished simply by changing the additives from NiI2 to HMPA during reductive cyclization conducted in H2O–THF. Total synthesis of (−)-kainic acid and (+)-allo-kainic acid, which are pyrrolidine alkaloids used in neuroscience and neuropharmacology as useful molecular probes, was successfully achieved by using the stereo-complementary ring closure reactions promoted by SmI2 for the construction of the 2,3,4-trisubsituted pyrrolidine scaffold of kainoids.

The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite.

A convenient and scalable synthesis of two unusual amino acid units found in dolastatin 16, dolaphenvaline, and dolamethylleuine, is described. Dolastatin 16, which was first isolated from the sea hare Dolabella auricularia by Pettit, exhibits not only strong inhibition of growth for a variety of human cancer cell lines but also potent antifouling activity against the larvae of the barnacle Balanus amphitrite. The key element of the synthesis is an organocatalytic Mannich reaction to construct two contiguous stereocenters in the amino acid units with almost complete enantio- and diastereoselectivity.

Chlorosulfolipids (CSLs) are an intriguing family of natural products featuring highly chlorinated linear hydrocarbon skeletons. Although CSLs were first isolated in 1962, chemical synthesis of CSLs was hampered because relevant methods for stereoselective construction of the polychlorinated motifs of CSLs were scarce. Since Carreira’s first total synthesis of the CSL mytilipin A in 2009, several groups, including our own, have reported total syntheses of CSLs. As a result of these total syntheses, important progress has been made in the development of reliable synthetic methods for stereoselective polychlorination. In this digest, we summarize the total syntheses of CSLs by focusing on synthetic methods for stereoselective polychlorination of the organic frameworks of CSLs.Figure optionsDownload full-size imageDownload as PowerPoint slide

A novel three-component coupling between trimethylsilylmethylphosphonate, acyl fluoride, and aldehyde has been developed. A sequential nucleophilic addition of lithio-trimethylsilylmethylphosphonate to the acyl fluoride and Horner–Wadsworth–Emmons reaction of an aldehyde with the lithio-β-ketophosphonate generated in situ by desilylation at the α-position of the α-silyl-β-ketophosphonate by fluoride took place cleanly in a one-pot operation. Various E- and Z-enones were obtained in high yields with high stereoselectivities by this one-pot procedure.

Asymmetric total synthesis of danicalipin A was achieved. The synthesis was characterized by diastereoselective introduction of chlorine atoms. Biological activities with synthetic danicalipin A, its enantiomer, and racemate were also evaluated toward brine shrimp. Both enantiomers of danicalipin A showed almost the same activity.

The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite.