Synthesis of Sphingosine Relatives, XVIII!. Synthesis of Penazetidine A, an Alkaloid Inhibitor of Protein Kinase C Isolated from the Marine Sponge Penares sollasi

Abstract

Two stereoisomers of penazetidine A (1a), the azetidine alkaloid isolated from the Indo‐Pacific marine sponge Penares sollasi, were synthesized by starting from (S)‐serine and (R)‐or (S)‐citronellol. The natural penazetidine A must be either (2S,3R,4S,12′R)‐ or (2S,3R,4S,12′S)‐1a.

Synthesis of Marine Bioregulators, Medicinals and Related Compounds

“…Its structure 155 was proposed on the basis of NMR and MS studies, although nothing was known about its absolute configuration. 18,19 For the synthesis of (2S,3R,4S,12 R)-penazetidine A (155), (S )-citronellol and (S )-Garner aldehyde (F) were employed as our starting materials. 18,19 For the synthesis of (2S,3R,4S,12 R)-penazetidine A (155), (S )-citronellol and (S )-Garner aldehyde (F) were employed as our starting materials.…”

Disproof of the Proposed Structures of Bradyoxetin, a Putative Bradyrhizobium japonicum Signaling Molecule, and HMCP, a Putative Ralstonia solanacearum Quorum-Sensing Molecule

“…Following this assumption, it is possible that the 166.4 ppm signal can be a carbonyl carbon and an oxygen or nitrogen in the side chain can be acylated. Although no proton nor carbon signal corresponding to the acyl chain was recorded in the 1 H and 13 C NMR spectra of bradyoxetin, some of its traces could be found in the reported HSQC and HMBC spectra. For instance, they observed a cross-peak between approximately 6.3 ppm of 1 H and 66 ppm of 13 C signals in the HSQC spectrum, even though these signals were not recorded in the 1D NMR spectra.…”

“…Although no proton nor carbon signal corresponding to the acyl chain was recorded in the 1 H and 13 C NMR spectra of bradyoxetin, some of its traces could be found in the reported HSQC and HMBC spectra. For instance, they observed a cross-peak between approximately 6.3 ppm of 1 H and 66 ppm of 13 C signals in the HSQC spectrum, even though these signals were not recorded in the 1D NMR spectra. This phenomenon leads us to hypothesize that the carbon atom of the acyl chain can be deuterated because it is well known that the reduction of the signal intensity by deuterium quadrupole relaxation or signal broadening due to residual C−D coupling is often observed in the 13 C NMR spectrum of a deuterated compound.…”

“…The slight chemical shift discrepancies might be caused by the concentration of the sample or the pH of the solution. This phenomenon is often observed when MeOH, a highly polar solvent, is used as the solvent for NMR . Although signals H-11 (6.21 ppm) and C-11 (67.1 ppm) were observed in the initial measurements, the signal intensities of these peaks were reduced after allowing the sample solution to stand for 2 weeks to promote the H–D exchange at C-11 (Figures S1 and S2).…”

“…For instance, they observed a cross-peak between approximately 6.3 ppm of 1 H and 66 ppm of 13 C signals in the HSQC spectrum, even though these signals were not recorded in the 1D NMR spectra. This phenomenon leads us to hypothesize that the carbon atom of the acyl chain can be deuterated because it is well known that the reduction of the signal intensity by deuterium quadrupole relaxation or signal broadening due to residual C−D coupling is often observed in the 13 C NMR spectrum of a deuterated compound. 12 In the process of estimating the bradyoxetin structure that satisfies (1) a p-disubstituted-phenyl moiety, (2) a nitro group and a sequential oxygen/nitrogen trisubstituted propyl chain, and (3) an acyl group with deuterium-exchangeable proton(s), we realize that chloramphenicol (10), a common antibiotic, can be a candidate for that compound.…”