“…Synthetic (±)− 1 exhibited ~60–70% efficacy of (–)− 1 , and synthetic (±)− 2 and (±)− 3 exhibited similar levels of efficacy with moderate IC 50 values. These in vitro results are consistent with those reported in the literature 7 , 53 , 63 . In an additional experiment, we found that all four diterpenoids could significantly increase the expression of cleaved poly (ADP-ribose) polymerase (PARP) (Supplementary Figure 2 ), indicating potential involvement of apoptosis.…”
Section: Resultssupporting
confidence: 93%
“…However, only two total syntheses of 7,20-epoxy- ent -kauranoids have been published including the pioneering work reported by Mander’s group on (±)-15-desoxy longikaurin C 49 , 50 and by Reisman’s group on (–)-longikaurin E 51 , 52 . Because of this, we have decided to develop a dependable synthesis towards 7,20-epoxy- ent -kauranoids, especially those with low isolation yields 53 , for a detail study of their anti-cancer activities. Fig.…”
Section: Introductionmentioning
confidence: 99%
“…The numbers in parenthesis indicate the amount that isolated from 10 kg of dried leaves of I. eriocalyx var. laxiflora 53 …”
Challenges in the development of anti-cancer chemotherapeutics continue to exist, particularly with respect to adverse effects and development of resistance, underlining the need for novel drugs with good safety profiles. Natural products have proven to be a fertile ground for exploitation, and development of anti-cancer drugs from structurally complex natural products holds promise. Unfortunately, this approach is often hindered by low isolation yields and limited information from preliminary cell-based assays. Here we report a concise and scalable synthesis of a series of low-abundance Isodon diterpenoids (a large class of natural products with over 1000 members isolated from the herbs of genus Isodon, which are well-known folk medicines for the treatment of inflammation and cancer), including eriocalyxin B, neolaxiflorin L and xerophilusin I. These scalable syntheses enable multilevel bio-evaluation of the natural products, in which we identify neolaxiflorin L as a promising anti-cancer drug candidate.
“…Synthetic (±)− 1 exhibited ~60–70% efficacy of (–)− 1 , and synthetic (±)− 2 and (±)− 3 exhibited similar levels of efficacy with moderate IC 50 values. These in vitro results are consistent with those reported in the literature 7 , 53 , 63 . In an additional experiment, we found that all four diterpenoids could significantly increase the expression of cleaved poly (ADP-ribose) polymerase (PARP) (Supplementary Figure 2 ), indicating potential involvement of apoptosis.…”
Section: Resultssupporting
confidence: 93%
“…However, only two total syntheses of 7,20-epoxy- ent -kauranoids have been published including the pioneering work reported by Mander’s group on (±)-15-desoxy longikaurin C 49 , 50 and by Reisman’s group on (–)-longikaurin E 51 , 52 . Because of this, we have decided to develop a dependable synthesis towards 7,20-epoxy- ent -kauranoids, especially those with low isolation yields 53 , for a detail study of their anti-cancer activities. Fig.…”
Section: Introductionmentioning
confidence: 99%
“…The numbers in parenthesis indicate the amount that isolated from 10 kg of dried leaves of I. eriocalyx var. laxiflora 53 …”
Challenges in the development of anti-cancer chemotherapeutics continue to exist, particularly with respect to adverse effects and development of resistance, underlining the need for novel drugs with good safety profiles. Natural products have proven to be a fertile ground for exploitation, and development of anti-cancer drugs from structurally complex natural products holds promise. Unfortunately, this approach is often hindered by low isolation yields and limited information from preliminary cell-based assays. Here we report a concise and scalable synthesis of a series of low-abundance Isodon diterpenoids (a large class of natural products with over 1000 members isolated from the herbs of genus Isodon, which are well-known folk medicines for the treatment of inflammation and cancer), including eriocalyxin B, neolaxiflorin L and xerophilusin I. These scalable syntheses enable multilevel bio-evaluation of the natural products, in which we identify neolaxiflorin L as a promising anti-cancer drug candidate.
“…Several ent -kauranoids with the same oxirane ring have been found in Isodon species (Figure S93, Supporting Information); however, the methods employed to resolve the chirality of C-16 were confusing and even contradictory among these compounds. For example, the NOE correlations between H 2 -17 and H-13 were used in the structure elucidation of both neolaxiflorin Y and maoyecrystal B; however, they were determined to have opposite configurations at C-16 (Figure S93, Supporting Information). To resolve the C-16 configuration of 7 , both 16 S *- 7 ( 7a ) and 16 R *- 7 ( 7b ) (Figure ) were subjected to quantum chemical calculation of the NMR chemical shifts.…”
Eight new diterpenoids (1–8) with
varied structures were isolated from the aerial parts of Isodon
xerophilus. Among them, xerophilsin A (1) was
found to be an unusual meroditerpenoid representing a hybrid of an ent-kauranoid and a long-chain aliphatic ester, xerophilsins
B–D (2–4) are dimeric ent-kauranoids, while xerophilsins E–H (5–8) are new ent-kauranoids.
The structures of 1–8 were elucidated
mainly through the analyses of their spectroscopic data. The absolute
configurations of 2, 6, and 8 were confirmed by single-crystal X-ray diffraction, and the configuration
of C-16 in 7 was established through quantum chemical
calculation of NMR chemical shifts, as well as modeling of key interproton
distances. Bioactivity evaluation of all isolated compounds revealed
that 2, 3, and 5 inhibited
NO production in LPS-stimulated RAW264.7 cells.
“…Neolaxiflorins I–Y, 17 novel ent -kaurane diterpenoids, were obtained from the Isodon eriocalyx var. laxiflora leaves (Yunnan, China), among which neolaxiflorin P ( 293 ) displayed the best activity against A-549, HL-60, MCF-7, SMMC-7721, and SW-480 cells with IC 50 ranges of 0.45–1.12 μM (Wang et al, 2015j ).…”
This review covers the literature published by chemists from China during the 2015–2016 on natural products (NPs), with 1,985 citations referring to 6,944 new compounds isolated from marine or terrestrial microorganisms, plants, and animals. The emphasis is on 730 new compounds with a novel skeleton or/and significant bioactivity, together with their source organism and country of origin.
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