Cinnamate sunscreens

IMI has recently issued several reports describing industrial applications of heterogeneous Heck catalysis for the manufacture of chemical building blocks [21-23]. This contribution focused on two classes of organic compounds in industrial use-cinnamates (sunscreens and intermediates for pharmaceuticals) and ben-zophenones (Scheme 2). 

Diglycol/CHDM/isophthalates/SIP copolymer sunscreen protectant, skin care Hydrolyzed lupine protein sunscreen vehicle, creams C12-15 alkyl benzoate sunscreen vehicle, oils C12-15 alkyl benzoate sunscreen, anti-UV-A Pansy (Viola tricolor) extract sunscreen, cosmetics TEA-salicylate sunscreen, topical p-Aminobenzoic acid Cinnamal sunscreening agent, cosmetics Guanine Homosalate suntan lamp monitors Thallium (I) chloride suntan lotions 3-Methylumbelliferone suntan preps. 

Sun worshipers and those who work outside can protect themselves from ultraviolet exposure with skin creams that contain UV-absorbing molecules. The UV-absorbing molecule in the first sunscreens was PABA, para-aminobenzoic acid. However, this compound may have toxic effects of its own. The UV-absorbing components of current sunscreens are derivatives of cinnamic acid and benzophenone. 

Sunscreens are transparent organic substances that penetrate into the skin and absorb ultraviolet radiation. Common classes of sunscreens include benzophe-nones, PABA derivatives, cinnamates, salicylates, and dibenzoylmethanesJ3 Ben-zophenones have a primary protective range in the UVA region and include oxy-benzone (Fig. 12.9.1), 270-350 nm dioxybenzone (Fig. 12.9.2), 206-380 nm ... 

An alternative approach to transdermal drug application that differs from patches and classic gels led to the foundation of Acrux, an Australian drug delivery company. The key finding was that certain widely used sunscreens, including Cs- to Cis-alkyl substituted-cinnamate,... 

Another very common use of phenolic compounds is in sunscreens. The presence of the aromatic ring results in the effective absorbance of the UV-B radiation (between 280 and 315 nm) from the sun and thus prevents sunburns. The most common active ingredient in many sunscreens is p-aminobenzoic acid (PABA 7.1), which is actually not a phenolic compound. This compound has been widely used since the 1970 s but is less popular nowadays due to the formation of skin rashes and acne. As a result many sunscreens are now PABA-free. Alternative active ingredients include salicylates such as octylsalicylate (7.2), cinnamates such as octyl methylcinnamate (7.3), benzophenone (7.4) and the related compound oxybenzone (7.5), and anthranilates, such as menthylanthranilate (7.6). Octyl methylcinnamate (7.3) is insoluble in water and is therefore commonly... 

Cinoiazepam [inn] is one of the [1,41 benzodiazepines, a BENZODIAZEPINE BINDING-SITE AGONIST, with most of its properties similar to diazepam. It has HYPNOTIC, ANTICONVULSANT and ANXIOLYTIC activity. It has been used orally to treat insomnia and anxiety, cinoxacin [ban, inn, jan, usan] (Clnobac ) is an ANTIMICROBIAL, One of a 4-quinolone family related to nalidixic acid, which, though symthetic, are sometimes described as ANTIBIOTICS. It can be used clinically as an ANTIBACTERIAL, mainly used orally for gut infections. Cinoxate [inn, usan] is a cinnamic acid derivative and can be used in topical sunscreen preparations. 

The chemical sunscreens approved for OTC use in the United States are classified into seven classes aminobenzoates (previously known as PABA and PABA derivatives), salicylates, cinnamates, benzophenones, an-thranilates, dibenzoylmethane derivatives, and one miscellaneous chemical (phenyl-ben-... 

Among all these UV-B Sunscreen agents octyl methoxy cinnamate accounts for almost 90% of all the Sunscreen agents and has been occupying a pride of place. Besides, octyl methoxy cinnamate (OMC) also known as 2-ethyl-hexyl cinnamate is produced from p-cresol via p-anisic aldehyde and will be discussed here in some detail. 

Soon p-anisic aldehyde produced from p-cresol through the process of methylation of the hydroxy group and subsequent oxidation of the methyl group, turned out to be a very important organic chemical and an attractive outlet of p-cresol. p-Anisic aldehyde is effectively used for making octyl methoxy cinnamate (an UV-B sunscreen chemical) and dilitiazem (an antihypertension drug). Subsequently, a series of downstream derivatives of p-cresol have been synthesized and commercially produced. 

In the last years, natural products have been used as antioxidative, melanogenesis inhibitors and sunscreen [48]. Lipid peroxidation is related to aging, membrane damage, heart disease, stroke and cancer in living organism. This oxidative mechanism could be stopped by the addition of synthetic anti-oxidants, but now it has been recognised that natural antioxidants are safe compared to tile synthetic compounds [49], Well-known natural anti-oxidants are represented by ubiquinones, tocopherols mid related compounds, flavonoids, cinnamic acid derivatives, licopene and related tetraterpenoids, and also by phenolic compounds [50]. 

Other examples for which homogeneously catalyzed Heck reactions have been exploited toward an industrial production include the preparation of the fragrance Lihal developed by Givaudan, the synthesis of the nonsteroidal anti-inflammatory drug Nabumeton by Hoechst-Celanese, ° and the synthesis of the sunscreen agent 2-ethylhexyl p-methoxy-cinnamate (EHMC) by Hoechst AG and other companies (Scheme 6). Noteworthy, Nabumeton is obtained in one step via coupling and domino isomerization reaction of 2-bromo-6-methoxynaphthalene with 3-buten-2-ol. ° ... 

Recently, some other derivatives have been used as sunscreen agents, e.g. esculin (109), 7-diethylamino-4-methylcoumarin and 2-ethoxy-ethyl p-methoxy-cinnamate (110). This latter compound was found to promote skin pigmentation by lengthening the exposure time to direct sunlight before the minimal erythema develops which is concomitant with the production of a lasting protective suntan. 

A number of chemical substances are effective at blocking UV radiation. An opaque cream of zinc oxide and titanium dioxide is the most effective type of sunscreen. In addition, para-aminobenzoic acid (PABA), benzophenone, and cinnamates are commonly used to block UV radiation. Recently, there has been a move away from the use of PABA, though. It s somewhat toxic, and a significant number of individuals are allergic to it. 

Scientists are working on sunscreen pigments. .. E. M. M. Tan et al. Excited-state dynamics of isolated and microsolvated cinnamate-based UV-B sunscreens. 2014. / Phys Chem Lett. 5(14), p. 2464. DOI 10.1021/jz501140b. 

PAA is an important precursor in the manufacture of OMC [2-ethylhexyl-p-methoxy-cinnamate (7), a UV adsorber in sunscreens] as well as of various pharmaceuticals, e.g., the coronary therapeutic Diltiazem (8) and chemotherapeutics like trimethoprim (9). ... 

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