The polyfused medium-sized CDE ring system of lancifodilactone G is assembled via B-alkyl Suzuki−Miyaura cross-coupling and SmI2-mediated pinacol macrocyclization as the key strategic steps.
An efficient entry to the ABC network of lancifodilactone G is outlined. The C ring is constructed by way of enyne ring-closing metathesis. The AB component is established via a base-mediated ...biomimetic oxy-Michael addition−lactonization sequence.
A detailed study to assess the enantioselectivity of the amino acid mediated intramolecular asymmetric aldol reaction of 1,3-cycloheptanedione bearing a C-2 methyl substituent has been undertaken. ...The cyclizations were mediated by a series of l-amino acids in the presence of an acid cocatalyst. Strikingly, the process is characterized by an inversion of enantioselectivity when compared to a similar reaction involving the 1,3-cyclohexanedione counterpart.
The richly oxygenated C(1)−C(30) polyol segment of amphidinol 3 has been synthesized in protected form. Incorporated in this long chain are 10 of the 25 stereogenic centers housed in the target. The ...asymmetric pathway that has been developed is based on the efficient union of three independently prepared subunits.
A stereochemically linear strategy has been developed to prepare the heavily congested F-ring sector of lancifodilactone G (1) from commercially inexpensive (R)-carvone. Prominent operations in our ...synthesis include Negishi-type sp2−sp3 cross-coupling and intramolecular free-radical cyclization for the purpose of appending the sidearm links of the D and H rings onto the F platform.
A program directed toward an asymmetric synthesis of pestalotiopsin A is described. The routing begins with the dextrorotatory cyclobutanol 37, which is combined with the enantiomerically defined ...building blocks ent-15 and 16. These units are incorporated via stereocontrolled 1,2-nucleophilic addition and anti-aldol coupling, respectively. With these straightforward reactions accomplished, the sequel involved the introduction of terminal double bonds in anticipation of the fact that the (E)-cyclononene substructure could be realized by ring-closing metathesis. This central issue was evaluated with several diene substrates and catalysts, all to no avail. Cross-metathesis experiments involving 59 and 65 with the functionalized heptene 60 revealed a marked difference in the inability to engage interaction with the ruthenium catalyst. This awkwardness could not be skirted.
A study designed to assess the diastereoselectivity of the intramolecular aldol reaction of two differently sized monocyclic 1,3-diketones bearing a chiral, oxygenated side chain has been undertaken. ...The cyclizations were brought about under catalysis by pyrrolidine, a series of d- and l-amino acids including proline, and several proline derivatives. The levels of selectivity were found to be consistently higher with the six-membered ring system than its cycloheptane counterpart.
Exhaustive dihydroxylation of the pair of cyclooctadienols consisting of 4 and 5, which are available in enantiomerically pure form from d-glucose, resulted in the formation of two diastereomeric ...tetraols in each case. The difference in polarity of the 6/7 and 8/9 pairs facilitated their chromatographic separation. Ensuing acetylation and PMB deprotection allowed for the assignment of relative (and ultimately absolute) stereochemistry to the resulting monohydric alcohols on the basis of J HH analysis of their 1H NMR spectra. The highly functionalized exomethylenecyclooctanes 14−17, which were derived by periodinane oxidation and Wittig olefination, were further elaborated by hydroboration and global deprotection. The eight members of the cyclooctanose family of carbasugars and their precursor intermediates consistently showed patterns of J HH values in line with the contiguous stereochemical relationships. Also assayed was their specific inhibitory behavior toward glycosidases.
An asymmetric synthesis of the heavily oxygenated inner sector of amphidinol 3 constituted of C31−C52 is described. The successful pathway highlights construction of the pair of identical ...tetrahydropyran subunits from a common intermediate.
