Conformational preferences of oxy-substituents in butenolide-tetrahydropyran spiroacetals and butenolide-piperidine spiro-N,O-acetals.

We describe the synthesis of a series of oxy-substituted butenolide spiroacetals and spiro-N,O-acetals by oxidative spirocyclisation of 2-[(4-hydroxy or 4-sulfonamido)butyl]furans. The axial-equatorial preference of each oxy-substituent is investigated (NMR) by an acid-catalysed thermodynamic relay of configuration between the spiro- and oxy-centres. The axial site is preferred for most oxy-substituents at synthetically useful levels. The potential origins of this preference are discussed in terms of a stabilising gauche effect combined with the influence of solvation. These results have relevance to the synthesis of bis(acetylenic)enol ether spiroacetals including AL-1 and related compounds.

Progress in the synthesis of the lituarines: stereocontrol in sequential C-C bond formation on a spirobutenolide template.

[structure: see text] We describe elaboration of a tricyclic spirobutenolide corresponding to the C(7-18) tricyclic substructure common to lituarines A-C. Conjugate addition, to install the C(16) methyl, is followed by construction of the crucial C(18-19) bond by silyl enol ether addition to the derived spiroacetal C(18)-O oxonium ion. Esterification with a C(1-6) acid, and selective ozonolysis to release the C(23) carbonyl, complete the assembly of all the carbons present in the lituarine macrocyclic core.

Syntheses of the C(1-6) and C(19-24) fragments of lituarines A, B, and C.

[structure: see text] Lituarines A-C are marine natural products comprising a tricyclic spiroacetal bridged at C(8) and C(18) by a functionalized ester linkage conceptually obtained from a C(19-24) alcohol and a C(1-6) carboxylic acid whose oxidation level varies at C(4) and C(5). Stereoselective routes are described to compounds 26 and 27, fully functionalized ester fragments of lituarine A and lituarines B and C, respectively.

Stereoselective synthesis of the lituarine tricyclic spiroacetal.

[reaction: see text] Oxidative cyclizations of 2-(4-hydroxybutyl)furan derivatives provide spirobutenolide acetals directly; on the basis of this methodology, we describe an asymmetric synthesis of a tricyclic spirobutenolide precursor to the C(7-18) fragment common to lituarines A-C.

Synthesis of pandamarilactone-1.

The first total synthesis of pandamarilactone-1, an alkaloid of Pandanus amaryllifolius, is reported. The nine-step synthesis features furan oxidation with singlet oxygen and then spiro-N,O-acetalization and elimination to generate the natural product and further Pandanus alkaloids, pandamarilactonines A-D.