The synthesis of (+)-monomorine I, an indolizidine alkaloid isolated from Monomorium pharaonis, has been achieved. The 2,6-cis-piperidine ring moiety of (+)-monomorine I was constructed using diastereoselective aminopalladation. Chain elongation via cross-metathesis using Hoveyda-Grubbs 2nd catalyst followed by deprotection of the Cbz group and cyclic reductive hydroamination afforded (+)-monomorine I.Download high-res image (47KB)Download full-size image

•First synthesis of legioliulin was accomplished.•Isocoumarin ring of legioliulin was constructed using cyclic acylpalladation.•Chain elongation was performed using Heck reaction using t-butylphosphine as a ligand.Concise synthesis of legioliulin, an isocoumarin compound isolated from Legionella dumoffii, was achieved. Isocoumarin ring of legioliulin was constructed using cyclic acylpalladation. Chain elongation was performed using Heck reaction using t-butylphosphine as a ligand.

Four diastereomers of tetradenolide, a cytotoxic α-pyrone isolated from Tetradenia riparia, were synthesized stereoselectively using the Z-selective Horner–Emmons reaction followed by acid catalyzed lactonization. Making comparison of the 1H and 13C NMR spectral data of the four diastereomers with those of the reported value of natural product did not lead to determine the relative stereochemistry of the natural tetradenolide. Thus detailed investigation of the spectral data of the related compounds led us to revise the structure of tetradenolide as deacetylboronolide.

(+)-Boronolide and (+)-deacetylboronolide were synthesized using Pd-catalyzed CO insertion and lactonization as the key step. As to the 13C NMR data of (+)-deacetylboronolide, the assignment at C-6 position should be revised.

The syntheses of (+)- and (−)-akolactone B and (+)-ancepsenolide were accomplished using a Pd-catalyzed carbonylation. As to the absolute configuration of akolactone B, making a comparison of the specific rotation of both enantiomers of synthetic akolactone B and the natural compound suggests that the absolute configuration at the 4-position of akolactone B is (R).(R)-(−)-Akolactone BC19H28O2[α]D18 = 38.1 (c 1.10, CHCl3)Source of chirality (R)-3-butyn-2-olAbsolute configuration: (2R)(+)-AncepsenolideC22H34O4[α]D18 = +47.1 (c 1.28, CHCl3)Source of chirality (S)-3-butyn-2-olAbsolute configuration: (2S, 19S)(2R,5E,17E)-Octadeca-5,15,17-trien-3-yn-2-olC18H28O[α]D19 = +15.9 (c 1.23, CHCl3)Source of chirality (R)-3-butyn-2-olAbsolute configuration: (2R)(2R,3Z,5E,15E)-4-Iodooctadeca-3,5,15,17-tetraen-2-olC18H29IO[α]D19 = +8.6 (c 1.69, CHCl3)Source of chirality (R)-3-butyn-2-olAbsolute configuration: (2R)(2S,19S)-2,19-Bis-(tert-butyldimethylsilyoxy)eicosa-3,17-diyneC32H62O2Si2[α]D18 = 5.4 (c 1.44, CHCl3)Source of chirality (S)-3-butyn-2-olAbsolute configuration: (2S, 19S)(2S,19S)-Eicosa-3,17-diyne-2,19-diolC20H34O2[α]D21 = 26.2 (c 0.635, CHCl3)Source of chirality (S)-3-butyn-2-olAbsolute configuration: (2S, 19S)(2S,19S)-4,17-Diiodoeicosa-3,17-diene-2,19-diolC20H36I2O2[α]D18 = 0.03 (c 1.25, CHCl3)Source of chirality (S)-3-butyn-2-olAbsolute configuration: (2S, 19S)

Synthesis of procyanidin B2 and B3 gallate derivatives, 3-O-gallate, 3″-O-gallate, and 3,3″-di-O-gallate, were synthesized using equimolar condensation mediated by Yb(OTf)3. Synthesized compounds showed significant antitumor effects against human prostate PC-3 cell lines. Their activities were weaker than well-known EGCG and prodelphinidin B3.

Total synthesis of prodelphinidin B1, B2, and B4 has been accomplished. The key step is Lewis acid-mediated equimolar condensations between an epigallocatechin and/or a gallocatechin nucleophile and an epigallocatechin and/or a gallocatechin electrophile. The antitumor effects of synthetic prodelphinidin B1–B4 against human PC-3 prostate cancer cell lines have been investigated. These compounds showed significant antitumor effects. Their activity seemed to be little bit stronger than EGCG and prodelphinidin B3, known antitumor agent.

Stereoselective syntheses of daedalin A and quercinol, an enantiomer of daedalin A, is described. The tyrosinase inhibitory activities of daedalin A and quercinol were examined. The activity of quercinol was weaker than that of daedalin A at high concentration.

The first synthesis of two possible diastereomers of tonkinelin was achieved. By comparison of the optical rotation of two candidates of tonkinelin and the natural compound, it is suggested that the absolute configuration of natural tonkinelin is likely to be (17S,18S). The inhibitory activity of these compounds was examined with bovine heart mitochondrial NADH–ubiquinone oxidoreductase. These compounds showed remarkably weak inhibitory activity compared to ordinary acetogenins such as bullatacin.