Marine Alkylpurines: A Promising Group of Bioactive Marine Natural Products

Abstract

Marine secondary metabolites with a purine motif in their structure are presented in this review. The alkylpurines are grouped according to the size of the alkyl substituents and their location on the purine ring. Aspects related to the marine source, chemical structure and biological properties are considered together with synthetic approaches towards the natural products and bioactive analogues. This review contributes to studies of structure-activity relationships for these metabolites and highlights the potential of the sea as a source of new lead compounds in diverse therapeutic fields.

Keywords: alkylpurines; antimicrobial activity; cytotoxicity; marine natural products; methylpurines; purines; terpenylpurines.

Figure 1

Structures of 1-methyladenine, herbipoline and related compounds.

Figure 2

Structure of several methylated guanines.

Figure 3

Structure of several methylated isoguanines.

Figure 4

Structure of mucronatine, 16, and methylmucronatine, 17.

Figure 5

Structure of nigricines 18–21.

Figure 6

Structure of methylated xanthines 22–26.

Figure 7

Structure of methylated 8-oxopurines 27 and 28.

Figure 8

Structure of methylated 8-oxopurines 29–32.

Figure 9

Structure of methylated 8-oxopurines 33–38.

Figure 10

Structure of agelasine.

Figure 11

Structure of malonganenones 39–46.

Figure 12

Structures of nuttingins 47–52.

Figure 13

Structure of agelasines E and F and related compounds 53–57.

Figure 14

Structure of agelasines A and B and analogues 58–62.

Figure 15

Structures of agelasines 63–69.

Figure 16

Structures of agelasines 70–72.

Figure 17

Structure of agelasines 73–77.

Figure 18

Structures of agelasines 78–84.

Figure 19

Structures of agelasimines A and B and gelasines A and B.

Figure 20

Structures of agelasines 89–93.

Figure 21

Structure of terpenylpurines 94–96.

Figure 22

Structures of asmarines 97–107.

Figure 23

Structures of alkylpurines 108–110.

Figure 24

Structures of purines 111–115.

Figure 25

Structures of alkylpurines 116–121.

Figure 26

Structures of alkylpurines 122–129.

Figure 27

Structures of spongosine and doridosine.

Figure 28

Structures of cyclonucleosides 132 and 133.

Figure 29

Structures of momusines 134–137.

Figure 30

Structures of hamiguanosinol and salvadenosine.

Figure 31

Structures of nucleosides 140–143.

Scheme 1

A general synthetic procedure towards 7-alkylpurines.

Scheme 2

Molinski’s synthesis of acremolin, 122 [91].

Scheme 3

Fujii’s synthesis of caissarone, 28, [120] and Itaya’s synthesis of aplidiamine, 113 [83].

Scheme 4

General retrosynthetic strategy for the synthesis of diterpenyladeninium derivatives.

Scheme 5

Gundersen’s synthesis of malonganenone J, 43 [131].

Figure 32

Structures of natural diterpenoids used in the synthesis of diterpenylpurines.

Scheme 6

Terpenylpurines obtained from trans-communic and cupressic acids and monoterpenes.

Scheme 7

Retrosynthetic schemes for asmarines.

Scheme 8

Synthesis of an advanced analogue of asmarine A by Shenvi [142].

Scheme 9

Molinski’s synthesis of salvadenosine, 139 [110].

Scheme 10

Molinski’s synthesis of hamiguanosinol, 138 [110].

Scheme 11

Synthesis of trachycladines A and B by Wu [143].

Scheme 12

Synthesis of trachycladines A and B and analogues by Koumbis [144,145].