Coupling of C9 - 14 (4) and C15 - 21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to 4/Cs2CO3/Pd(dppf)2). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki−Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric β-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8 - 9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still−Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7 - 24 (7) ready to be coupled with the C1 - 6 fragment, which is described in Part 2 of this series.

(2017) A new topical panthenol-containing emollient: Results from two randomized controlled studies assessing its skin moisturization and barrier restoration potential, and the effect on skin microflora, Journal of Dermatological Treatment, 28:2, 173-180, DOI: 10.1080/09546634.2016 Purpose: Two randomized, intra-individual comparison studies were performed in healthy subjects to evaluate the skin moisturization and barrier restoration potential of a new topical panthenol-containing emollient (NTP-CE) (Study 1), and its effect on skin microflora (Study 2). Methods: In Study 1 (N ¼ 23), two skin areas, one challenged with 0.5% sodium dodecyl sulfate (SDS) solution and one unchallenged, were treated with NTP-CE for 3 weeks. Transepidermal water loss (TEWL), skin hydration, and intercellular lipid lamellae (ICLL) organization were measured at regular intervals during the study. In Study 2 (N ¼ 20), quantitative bacterial cultures were obtained over 6 h from a skin area undergoing wash stress with 10% SDS with subsequent single application of NTP-CE. Results: In Study 1, mean AUC for TEWL reduction from baseline was more pronounced with NTP-CE compared with control (À168.36 vs. À123.38 g/m 2 /h, p ¼ 0.023). NTP-CE use was also associated with statistically significant improvements in stratum corneum hydration and an increase in mean ICLL length from baseline (day 22: 120.61 vs. 35.85 nm/1000 nm 2 , p < 0.001). In Study 2, NTP-CE use had no negative impact on bacterial viability. Conclusions: NTP-CE use has favorable and lasting effects on barrier function and repair as well as skin hydration without negatively influencing bacterial viability. ARTICLE HISTORY

Purpose: Two studies were conducted with a new topical panthenol-containing emollient (NTP-CE) to investigate the skin-moisturizing effect in healthy adults and tolerability in healthy infants. Methods: In Study 1 (N ¼ 44), a single skin application of NTP-CE was performed followed by a 4-week twice-daily application. Skin hydration and stratum corneum (SC) water content change (using Raman spectroscopy) were measured. In the 4-week Study 2 (N ¼ 65, aged 3-25 months), NTP-CE tolerability was assessed using a 5-point scoring system; skin hydration was determined in a subset (N ¼ 21). Results: In Study 1, mean AUC 0 À 24 h for skin capacitance change from baseline was 302.03 i.u. with NTP-CE and À15.90 i.u. in control areas (p < .001). With NTP-CE (at 4 h), the water content within the upper SC part was reduced (À45.10 vs. À13.39 g/cm 2 , p ¼ .013) and the water gradient increased (0.51 vs. 0.11 g/ cm 4 , p ¼ .036), indicating relocation of water into deeper layers. In Study 2, there was no statistically significant change from baseline in mean cutaneous tolerability scores. At days 7, 14, and 28, skin hydration had increased by 42%, 54%, and 49%, respectively (all p < .001). Conclusions: Single and prolonged NTP-CE usage is associated with sustained and deep skin moisturization. NTP-CE is well tolerated by healthy infants. ARTICLE HISTORY

Three studies were conducted with three new dexpanthenol-containing emollients containing increasing lipid contents (Emollients 1–3) to assess their performances in healthy adults with dry skin. All three studies (N = 42 each) followed virtually the same design. A single skin application of the study product was performed followed by once-daily usage. Skin hydration, transepidermal water loss (TEWL), skin biomechanical properties, and lipid content of the stratum corneum (SC) were regularly assessed over the 28-day study period; a subset (N = 22) underwent a sodium lauryl sulfate (SLS) challenge prior to product application. All three emollients were well tolerated and showed good performances with only minor differences in instrumental measurements. After single and prolonged once-daily applications of Emollients 1–3 to dry skin and dry SLS-damaged skin, skin hydration significantly increased from baseline (BL) (by 38.1–72.4% in unchallenged skin, p < 0.001 for all three). This was paralleled by significant increases in skin elasticity parameters. Usage of Emollients 1 and 3 caused increases from BL in SC cholesterol (by 9.8–12.5%, p < 0.05 for both) and SC free fatty acid levels (by 3.7–26.3%, p < 0.05 for both) at the end of the study. No sustained effects on TEWL were recorded. Our findings support the once-daily use of all three emollients in adults with dry skin.

Our results indicate that NTP-CE is efficacious and safe when used for maintenance treatment of mild childhood AD.