Armin Guggisberg

Macrocyclic spermidine and spermine alkaloids

In this short review of spermine and spermidine plant alkaloids, which are characterized by the presence of a macrocyclic Iactam ring, special consideration has been given to the alkaloids from Oncinotis species and to the spermine alkaloid, chaenorrhine.

Macrocyclic Spermine Alkaloids from Verbascum: The (E/Z)-Isomeric Pairs (−)-(S)-Verbasitrine/(−)-(S)-Isoverbasitrine and (+)-(S)-Verbametrine/(+)-(S)-Isoverbametrine: Isolation, Structure Elucidation, and Synthesis

The isolation and structure elucidation of the 17-membered macrocyclic spermine alkaloids (−)-(S)-verbasitrine (2), (−)-(S)-isoverbasitrine (4), (+)-(S)-verbametrine (6), and (+)-(S)-isoverbametrine (8) is presented. The synthesis of their racemates is described.

Putrescine, spermidine, spermine, and related polyamine alkaloids.

Publisher Summary This chapter discusses the chemistry, biological, and pharmacological aspects of putrescine, spermidine, spermine, and related polyamine alkaloids. Aliphatic di- and polyamines are widespread in microorganisms, plants, and animals, as conjugates to a number of different biological structures, and also in free form. They are known since; Lewenhoeck examined a linear tetra-amine derivative obtained from sperm, spermine phosphate. In addition to the almost ubiquitous spermine, and the two equally abundant compounds putrescine and spermidine, a great number of other biogenic di-, tri-, and tetra-amine compounds are known. Among these, sym -nor-spermidine, homospermidine, sym-homospennidine, and sym-homospermine are of particular relevance for this treatise because they occur together with putrescine, spermidine, and spermine as fundamental building blocks in polyamine alkaloids. For pharmacological studies, two biological properties of the polyamines and their derivatives are of significance. The first concerns the influence of polyamines on cell proliferation, which makes the polyamines and their derivatives interesting compounds for investigations in the field of neoplastic diseases. The second concerns the interactions of polyamines with ion channels and related receptors, which is interesting with regard to diseases of the central nervous system. With respect to cancer research, the biosynthetic enzymes of polyamines were considered as promising targets for chemotherapy. In particular, spermidine/spermine N 1 -acetyltransferase, the highly regulated key enzyme of polyamine degradation, represents a new target for novel antineoplastic agents. Many synthetic analogs of the natural polyamines have been tested as agents against different cancers, and in some cases the results are rather promising. The interaction of polyamines with ion channels is of central importance for neurotransmittance.

O(2),1,9-trimethyluric acid and 1,3,7,9-tetramethyluric acid in leaves of different Coffea species

Abstract O (2),1,9-Trimethyluric acid and 1,3,7,9-tetramethyluric acid were isolated from young leaves of Coffea liberica , C. arnoldiana , C. dewevrei var. excelsa and var. aruwimiensis . The first purine has not been found before in nature; its identification required the synthesis of nearly all of its possible isomers.

Synthesis of the spermidine alkaloid (±)-N-acetyl-N(1)-deoxymayfoline

Abstract The total synthesis of the spermidine alkaloid (±)-N(1)-acetyl-N(1)-deoxymayfoline ((±)-1) was achieved by expansion of rings. The 5-membered cyclic compound 2was fused with butadiene by intermolecular Diels-Alder cycloaddition. The resulting 7-phenyl-1,6-diazabicyclo[4.3.0]nona-3,7-dien-9-one (4) was reductively cleaved with Raney-Ni in alcoholic KOH to afford the mono-cyclic lactam 6. This was selectively alkylated in high yields to the cyano derivative 7. Reduction of the nitrile group to the amine derivative 8 went smoothly by use of Adams catalyst in the presence of acid. Intramolecular transamidation was then accomplished by acid catalysis with TsOH to furnish the 13-membered diazalactam 9. The synthesis of (±)-1 was completed by the selective acetylation of the more nucleophilic amino group.

Protoverbine, the Parent Member of a Class of Macrocyclic Spermine Alkaloids

The 17-membered macrocyclic spermine alkaloids protoverbine ((8S)-8-phenyl-1,5,9,13-tetraazacycloheptadecan-6-one, 1) and its N(9),N(13)-methylene-bridged derivative protomethine ((2S)-2-phenyl-1,5,9,14-tetraazabicyclo[12.3.1]octadecan-4-one, 2) were isolated from Verbascum pseudonobileStoj.etStef. (Scrophulariaceae) and characterized. The synthesis of their racemates is described. The possible role of (S)-protoverbine (1) and (S)-protomethine (2) as precursors in the biogenesis of the whole class of N(1),N(9)- and/or N(13)-substituted alkaloids, the groups of verbamethine ((S)-3a – f), verbacine ((S)-4a – f), incasine B′/verdoline ((S)-5a – f), verbamedine ((S)-6a – f), and verbascenine ((S)-7a – f), is discussed.

Synthesis and selective deprotection of the penta-N-protected polyamine 1,16-diamino-4,8,13-triazahexadecane

Abstract The synthesis of the penta-N-protected polyamine thermopentamine (PA 3343, 1a, tert-butyl N-[4-benzyl-16-diallylamino-13-(pyridine-2-suilfonyl)-9-trifluoroacetyl-4,9,13-triazahexadec-1-yl]-carbamate), containing five different N-protecting groups is described. These protecting groups include tert-butoxycarbonyl, benzyl, trifluoroacetyl, diallyl, and pyridine-2-sulfonyl. In spite of the syntheses of specific polyamine derivatives the selective removal of each of these groups has been investigated.

The systematic position of theHolarrheninae (Apocynaceae)

AbstractThe genusHolarrhena, described byRobert Brown in 1811, has had a problematic taxonomic history, in part due to a suite of characters that does not conform with accepted concepts within theApocynaceae. In a number of important taxonomic charactersHolarrhena is typical of subfam.Apocynoideae. But due to the relatively unspecialized structure of the anthers most recent authors have placedHolarrheng, together withCarruthersia andSpirolobium, as the subtribeHolarrheninae in subfam.Plumerioideae. For the present investigation the floral structure and pollen morphology ofHolarrhena, Carruthersia andSpirolobium were analyzed. From the chemical literature reports of the occurrence of steroidal alkaloids in thePlumerioideae were evaluated. Our results indicate that the three genera belong to subfam.Apocynoideae in the tribeNerieae, but that the “Holarrheninae” is an unnatural group, and that the three genera should be accommodated individually within the tribe.

Chemotaxonomic study of the genusTabernaemontana (Apocynaceae) based on their indole alkaloid content

According to their alkaloidal products species of the “new” genusTabernaemontana can be partly differentiated. This differentiation is in agreement with the “old” genera classification. From the chemotaxonomic point of view a subdivision of subfam.Plumerioideae of theApocynaceae is proposed.

Crystal structure of mozambioside, a diterpene glycoside of Coffea pseudozanguebariae

Abstract A diterpene glycoside of the furokaurane type has been isolated from the seeds of the caffeine-free coffee species Coffea pseudozanguebariae belonging to the section Mozambicoffea. This bitter-tasting compound named mozambioside is considered to replace caffeine with respect to chemical defence. Its configuration was determined by means of X-ray diffraction analysis.