Complex Biohopanoids Synthesis: Efficient Anchoring of Ribosyl Subunits onto a C₃₀ Hopane

Abstract

Bacteriohopanoids represent a particularly important series of triterpenoids, widely distributed in bacteria. One of the common features of these pentacyclic hopanepolyols is the presence of an extended non-terpenoid and polyhydroxylated side chain attached to the triterpenic moiety through a C--C bond. The biological function of biohopanoids also has to be addressed when one considers the broad diversity in both structures and functionalities found in the side chain. Moreover, the stereochemistries of some biohopanoids are still unconfirmed, due to the lack of synthetic methods to prepare them. In this study we describe an efficient methodology for the formation of the C--C bond between the C(30)-hopane component and C(5)-polyhydroxylated carbohydrates through the use of a hopanyllithium intermediate, which has enabled us to synthesize several biohopanoid derivatives. We also report the first synthesis of hopanepentol bearing an additional hydroxy group at position C31.

Diastereoselective Synthesis of Aminobacteriohopanetetrol, a Biomarker for Methanotrophic Bacteria: Confirmation of the Absolute Configuration

“…(31R)-9) (136.0 mg, 0.2 mmol) [16] in a mixture of THF (2 ml) and DMF (1 ml) under Ar atmosphere was added NaH (60%; 40.0 mg, 1.0 mmol) portionwise at 08, and suspended at this temp. for 30 min.…”

“…C-NMR correlations were performed to assign the chemical shifts of the C 5 side chain of 1, the hopane framework being numbered as shown in Fig. 1, and assigned as described in [16]. Mass spectra were recorded in the electron-impact (EI), chemical-ionization (CI), or fast-atom-bombardment (FAB) modes on a JMS-700 mass spectrometer; in m/z.…”

“…After LiDBB-promoted lithiation followed by coupling with aldehyde 8, we obtained the alcohol 9 in 81% yield, with a 7 : 1 diastereoisomer ratio of (31R)-9/(31S)-9. After benzylation, the two epimers were separated, and the absolute configuration at C(31) of the major isomer was unambiguously demonstrated through the transformation of (31R)-9 into a pyranoside [16].…”

“…Recently, we have reported a concise strategy centered on the copper (Cu) activation of the C 30 hopane moiety for the synthesis of bacteriohopanetetrol and its glycosylated derivative [15]. Then, we developed a more general approach based on lithiation with lithium 4,4'-di-(tert-butyl)biphenylide (LiDBB) for the synthesis of a wide range of biohopanoids, including bacteriohopanepentols bearing an additional OH group at C(31) (Scheme 1) [16]. This key metalation step led us to prepare the natural biohopanoids 5a and 5b as well as the ribosyl-hopane 6a, a putative biosynthetic intermediate of the biohopanoid CHEMISTRY & BIODIVERSITY -Vol.…”

“…Results and Discussion. 1 ) -The synthesis of 1 is outlined in Scheme 2, and started from the sulfide 7b [16], which was obtained in four steps from 22-hydroxyhopan-3-one, which, in turn, had been extracted from the commercially available dammar resin [17]. After LiDBB-promoted lithiation followed by coupling with aldehyde 8, we obtained the alcohol 9 in 81% yield, with a 7 : 1 diastereoisomer ratio of (31R)-9/(31S)-9.…”