Application of Cp₂TiCl-Promoted Radical Cyclization: A Unified Strategy for the Syntheses of Iridoid Monoterpenes

Abstract

An expedient approach toward the unified total syntheses of (+)-iridomyrmecin, (-)-isoiridomyrmecin, (+)-7- epi-boschnialactone, (+)-teucriumlactone, and (-)-dolichodial in chirally pure forms starting from readily available (+)-β-citronellene is delineated combining step economy and simplicity. Highlights include a Ti(III)-mediated reductive epoxide opening-cyclization for the construction of the core cyclopenta[ c]pyran skeleton of the iridoid lactones with complete diastereoselectivity for the newly created bridgehead stereogenic centers. Subsequent transformations facilitate a short access to (+)-teucriumlactone and (-)-dolichodial and formal access to potentially other iridoids.

Cytotoxic and Anti-inflammatory Terpenoids from the Whole Plant of Vaccinium emarginatum

“…The iridomyrmecintype boat form ( 1 B 4 ) of 21 was deduced from the negligible coupling between Hα-1 and H-7a and the coupling constant of 3.8 Hz between Hβ-1 and H-7a, which was consistent with the data in the literature assigned to iridomyrmecin-type analogs [28][29][30][31]. In contrast, Hα-1 and H-7a exhibits a larger coupling constant (11 Hz) in the isoiridomyrmecin-type boat form [28][29][30]32]. Because the carbonyl functionality in the iridomyrmecin-type boat form is folded and located closer to the cyclopentane ring (▶ Fig.…”

“…In accordance with the fragment obtained from the COSY spectrum (▶ Fig. 2), 21 was reminiscent of the structure of iridomyrmecin (or isoiridomyrmecin) [28], with the exception of the replacement of a methyl by a hydroxymethyl group. Detailed interpretation of the HMBC spectrum (▶ Fig.…”

“…Accordingly, 21, which has the same configurations at C-4, C-4a, C7, and C-7a as iridomyrmecin and a consistent optical rotation ( (OH) and 1732 cm −1 (δlactone). Despite the similarities of the IR, MS, and 13 C NMR data of these two compounds, the 1 H NMR spectrum (▶ Table 3 the literature [28][29][30]32]. In accordance with isoiridomyrmecintype analogs, the hydroxymethyl at C-4 was located in the β-pseudo-equatorial position, which was confirmed by the coupling constant of 10.9 Hz between H-4 and H-4a.…”

Application of Pauson–Khand reaction in the total synthesis of terpenes

“…88 Some of them are accomplished and reported by Suh and co-workers 89,90 and recently one reported by Chakraborty and co-workers. 91 In spite of the appearance of these reports among the others, a literature survey disclosed few reports on the total synthesis of diverse oxy-functionality pattern observed on the cyclopentane ring of the iridoid framework. 89,92,93 In 2019, Khan and co-workers reported an efficient and economic strategy to have access to several iridoids (65, 68, 68 0 , 70, 71, 72, 75, 75 0 , 79) 94 using an intramolecular Pauson-Khand reaction (IPKR) as the crucial step to access ten iridoids in a stereoselective fashion.…”

Recent Advances in Iridoid Chemistry: Biosynthesis and Chemical Synthesis

“…Chakraborty and coworkers have developed a methodology to construct a bicyclic δ ‐lactone, which is applied to the synthesis of iridoid monoterpenes 5 , 6 , 93 – 99 (Scheme 10). [42] The cis ‐fused cyclopentano lactone is built via Ti(III)‐mediated radical cyclization [43] . When the epoxy ester 100 , which is derived from (+)‐β‐citronellene in three steps, is treated with Cp 2 TiCl 2 in the presence of activated Zn dust, isoiridomyrmecin ( 93 ) and iridomyrmecin ( 5 ) are synthesized via the transition state 101 .…”