William H. C. Martin

Total synthesis of solandelactones A, B, E, and F exploiting a tandem Petasis-Claisen lactonization strategy.

Solandelactones A, B, E, and F were synthesized using Nozaki-Hiyama-Kishi coupling of iododiene 13 with aldehydes 14 and 99 obtained by oxidation of alcohols 92 and 94. Key steps in the synthesis of 92 and 94 were (i) a Nagao asymmetric acetate aldol reaction of aldehyde 77 with thionothiazolidine 78 to set in place an alcohol that becomes the (7 S) lactone center of solandelactones, (ii) a Simmons-Smith cyclopropanation of 80 directed by this alcohol, and (iii) Petasis methylenation of cyclic carbonate 90 in tandem with a Claisen rearrangement that generates the octenalactone portion of solandelactones. Synthesis of solandelactones A, B, E, and F confirmed their gross structure and absolute configuration at C7, 8, 10, and 14 but showed that alcohol configuration at C11 must be reversed in pairs, A/B and E/F, from the previous assignment made to these hydroid metabolites. Thus, solandelactones A and B are correctly represented by 2 and 1, respectively, whereas solandelactones E and F are 6 and 5. A biogenesis of solandelactones is proposed for these C 22 oxylipins that parallels a hypothesis put forward previously to explain the origin of C 20 cyclopropane-containing algal products.

Revisiting the Maitland–Japp reaction. Concise construction of highly functionalised tetrahydropyran-4-ones

Application of modern synthetic methods to the Maitland-Japp reaction has provided a one pot, one step procedure for the efficient construction of highly substituted tetrahydropyran-4-ones.

The one-pot, multi-component construction of highly substituted tetrahydropyran-4-ones using the Maitland-Japp reaction.

A one-pot, multi-component reaction for the synthesis of highly substituted tetrahydropyran-4-ones, based on the long forgotten Maitland-Japp reaction has been realised. Two different aldehydes and a derivative of a beta-ketoester can be condensed regioselectively in the presence of a Lewis acid to form tetrahydropyran-4-ones in excellent yields. The diastereoselectively of the reaction was found to be dependant upon the nature of the Lewis acid and the temperature at which the reaction was carried out. This procedure was also extended to the formation of tetrahydropyran-4-ones in greater than 95% enantiomeric excess.

Synthesis of an Advanced Intermediate for (+)-Pillaromycinone. Staunton−Weinreb Annulation Revisited

Condensation of an orsellinate anion with a 2-cyclohexenone (Staunton-Weinreb annulation) afforded a linear tetracycle which was converted to a protected derivative of 12a-epipillaromycinone. Methodology for introducing a 12a-hydroxyl substituent into the tetracycle with correct (R) configuration is described.

Organic residue analysis of Egyptian votive mummies and their research potential

Vast numbers of votive mummies were produced in Egypt during the Late Pharaonic, Ptolemaic, and Roman periods. Although millions remain in situ, many were removed and have ultimately entered museum collections around the world. There they have often languished as uncomfortable reminders of antiquarian practices with little information available to enhance their value as artefacts worthy of conservation or display. A multi-disciplinary research project, based at the University of Manchester, is currently redressing these issues. One recent aspect of this work has been the characterization of natural products employed in the mummification of votive bundles. Using gas chromatography–mass spectrometry and the well-established biomarker approach, analysis of 24 samples from 17 mummy bundles has demonstrated the presence of oils/fats, natural waxes, petroleum products, resinous exudates, and essential oils. These results confirm the range of organic materials employed in embalming and augment our understanding of the treatment of votives. In this first systematic initiative of its kind, initial findings point to possible trends in body treatment practices in relation to chronology, geography, and changes in ideology which will be investigated as the study progresses. Detailed knowledge of the substances used on individual bundles has also served to enhance their value as display items and aid in their conservation.

Accelerated generation of (protonated) imines and quinoxalines by formation of C=N bonds in the microdroplets of a nebuliser

Ions corresponding to protonated imines appear in the positive ion electrospray mass spectra of mixtures of the parent aromatic aldehyde and arylamine. The formation of these imine products occurs readily in the electrospray source nebuliser, even without the application of a spray potential. This accelerated formation of C=N bonds in the nebuliser has been extended to encompass the preparation of quinoxalines from a range of substituted phenylenediamines and benzils. The condensation may be induced either under conventional positive ion electrospray conditions (to give the protonated quinoxalines) or when the nebuliser is disconnected from the mass spectrometer (to give the neutral quinoxaline). Ions corresponding to intermediate adducts formed by condensation of the phenylenediamine component with the protonated benzil are observed in many cases when the condensation occurs in the mass spectrometer. This finding supports an interpretation based on nucleophilic addition in droplets generated by the nebuliser.

The Mechanism of Alkene Elimination from Protonated Toluenesulphonamides Generated by Electrospray Ionisation

The positive ion electrospray mass spectra of a range of sulphonamides of general structure CH3C6H4SO2NHR1 [R1 = C n H2n+1 (n = 1–7), C n H2n-1 (n = 3, 4), C6H5, C6H5CH2 and C6H5CH(CH3)] and CH3C6H4SO2NR1R2 [R1, R2 = C n H2n+1 (n = 1–8)] are reported and discussed. The protonated sulphonamides derived from saturated primary and secondary aliphatic amines generally fragment to only a limited extent unless energised by collision. Two general fragmentations are observed: firstly, elimination of an alkene, C n H2n, obtained by hydrogen abstraction from one of the C n H2n+1 alkyl groups on nitrogen; secondly, cleavage to form CH3C6H4SO2+. The mechanism by which an alkene is lost has been probed by studying the variation of the intensity of the [M + H – C n H2n]+ signal with the structure of the alkyl substituent(s) on nitrogen and by monitoring the competition between the loss of different alkenes from protonated unsymmetrical sulphonamides in which two different alkyl groups are attached to nitrogen. This fragmentation is favoured by branching of the alkyl group at the carbon atom directly attached to nitrogen, thus suggesting that it involves a mechanism in which the stability of the cation obtained by stretching the bond connecting the nitrogen atom to the alkyl group is critical. This interpretation also explains the competition between alkene elimination and cleavage to form CH3C6H4SO2+ (and, in some cases, cleavage to form C6H5CH2+ or [C6H5CHCH3]+).

Application of positive mode atmospheric chemical ionisation to distinguish epimeric oleanolic and ursolic acids.

A new and more reliable method is reported for distinguishing the equatorial and axial epimers of oleanolic and ursolic acids and related triterpenoids based primarily on the relative abundance of the [M + H]+ and [M + H – H2O]+ signals in their positive mode atmospheric pressure chemical ionisation mass spectra. The rate of elimination of water, which is the principal primary fragmentation of protonated oleanolic and ursolic acids, depends systematically on the stereochemistry of the hydroxyl group in the 3 position. For the β-epimer, in which the 3-hydroxyl substituent is in an equatorial position, [M + H – H2O]+ is the base peak. In contrast, for the α-epimer, where the 3-hydroxyl group is axial, [M + H]+ is the base peak. This trend, which is general for a range of derivatives of oleanolic and ursolic acids, including the corresponding methyl esters, allows epimeric triterpenoids in these series to be securely differentiated. Confirmatory information is available from the collision-induced dissociation of the [M + H – H2O]+ primary fragment ions, which follow different pathways for the species derived from axial and equatorial epimers of oleanolic and ursolic acids. These two pieces of independent spectral information permit the stereochemistry of epimeric oleanolic and ursolic acids (and selected derivatives) to be assigned with confidence without relying either on chromatographic retention times or referring to the spectra or other properties of authentic samples of these triterpenoids.

2 Synthetic methods

This report surveys significant developments in the field of protecting group chemistry over the calendar year 2002. As the chemistry of protecting groups is vast, even within the limitation of one year, it would be impossible to provide a complete and comprehensive summary in the space allocated. We have therefore exercised a certain amount of discretion in selecting what we consider to be the most significant of the achievements in this area over 2002. To this end we have included sections on the developments of protecting group strategies for carbohydrates, peptides and DNA bases. We have also included a section on protecting groups in the synthesis of larger target molecules, trying where appropriate to highlight those cases where the protecting group influences the outcome of a reaction in either an anticipated or an unexpected manner (Section 9).