A decade review of triphosgene and its applications in organic reactions.

This review article highlights selected advances in triphosgene-enabled organic synthetic reactions that were reported in the decade of 2010-2019. Triphosgene is a versatile reagent in organic synthesis. It serves as a convenient substitute for the toxic phosgene gas. Despite its first known preparation in the late 19th interestingly began only three decades ago. Despite the relatively short history, triphosgene has been proven to be very useful in facilitating the preparation of a vast scope of value-added compounds, such as organohalides, acid chlorides, isocyanates, carbonyl addition adducts, heterocycles, among others. Furthermore, applications of triphosgene in complex molecules synthesis, polymer synthesis, and other techniques, such as flow chemistry and solid phase synthesis, have also emerged in the literature.

Brønsted Acid Catalyzed Synthesis of Functionalized 1,4- and 1,6-Dicarbonyl Monosilyl Enol Ethers under Operationally Practical Conditions.

Herein, we report an improved protocol for the concise synthesis of functionalized 1,4- and 1,6-dicarbonyl-derived monosilyl enol ethers via ionization of α'-hydroxy silyl enol ethers to generate unsymmetrical silyloxyallyl cations that were subsequently captured by TBS silyl enolates. These transformations were efficiently performed in acetonitrile at room temperature by employing pyridinium triflate as a catalyst. Our new reaction conditions are operationally more practical and broaden the accessibility of various 1,4- and 1,6-dicarbonyl groups, which include diketone, ketoester, and ketothioester functionalities.

Comparing calvarial transport distraction with and without radiation and fat grafting.

The purpose of this study is to: a) assess transport distraction to reconstruct cranial defects in radiated and non-radiated fields b) examine adipose grafting's effect on the bony regenerate and overlying wound, and c) elucidate sources of bone formation during transport distraction osteogenesis. Twenty-three male New Zealand white rabbits (3 months; 3.5 kg) were used, 10 non-irradiated and 13 irradiated (17 treatment, 6 control) with a one-time fraction of 35 Gy. A 16 × 16 mm defect was abutted by a 10 × 16 mm transport disc 5 weeks after irradiation, and 11 animals were fat grafted at the distraction site. Latency (1 day), distraction (1.5 mm/day), and consolidation (4 weeks) followed. Fluorochromes were injected subcutaneously and microCT, fluorescence, and histology assessed. In distracted animals without fat grafting, bone density measured 701.87 mgHA/ccm and 2271.95 mgHA/ccm in irradiated and non-irradiated animals. In distracted animals with fat grafting, bone density measured 703.23 mgHA/ccm and 2254.27 mgHA/ccm in irradiated and non-irradiated animals. Fluorescence revealed ossification emanating from the dura, periosteum, and transport segment with decreased formation in irradiated animals. Transport distraction is possible for cranial reconstruction in irradiated fields but short-term osseous fill is significantly diminished. Adipose grafting enhances wound healing in previously irradiated fields but does not enhance ossification.

Evaluation of cranial bone transport distraction with and without adipose grafting.

Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.

Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme.

Parathyroid hormone-related protein (PTHrP) regulates cell fate and specifies the mammary mesenchyme during embryonic development. Loss of PTHrP or its receptor (Pthr1) abolishes the expression of mammary mesenchyme markers and allows mammary bud cells to revert to an epidermal fate. By contrast, overexpression of PTHrP in basal keratinocytes induces inappropriate differentiation of the ventral epidermis into nipple-like skin and is accompanied by ectopic expression of Lef1, ß-catenin and other markers of the mammary mesenchyme. In this study, we document that PTHrP modulates Wnt/ß-catenin signaling in the mammary mesenchyme using a Wnt signaling reporter, TOPGAL-C. Reporter expression is completely abolished by loss of PTHrP signaling and ectopic reporter activity is induced by overexpression of PTHrP. We also demonstrate that loss of Lef1, a key component of the Wnt pathway, attenuates the PTHrP-induced abnormal differentiation of the ventral skin. To characterize further the contribution of canonical Wnt signaling to embryonic mammary development, we deleted ß-catenin specifically in the mammary mesenchyme. Loss of mesenchymal ß-catenin abolished expression of the TOPGAL-C reporter and resulted in mammary buds with reduced expression of mammary mesenchyme markers and impaired sexual dimorphism. It also prevented the ectopic, ventral expression of mammary mesenchyme markers caused by overexpression of PTHrP in basal keratinocytes. Therefore, we conclude that a mesenchymal, canonical Wnt pathway mediates the PTHrP-dependent specification of the mammary mesenchyme.