Appendageal Structures

Appendageal structures commonly found within the skin are the hairs, hair follicles, associated sebaceous glands, apocrine and eccrine sweat glands, and arrector pili muscles. Hairs are formed by epidermal invaginations. These keratinized structures traverse the dermis and may extend into the hypodermis. The free part of the hair above the surface of the skin is the hair shaft, and the part deep within the dermis is the hair root, which forms an expanded knob-like structure called the hair bulb. This is composed of a matrix of epithelial cells in different stages of differentiation. Hair is composed of three concentric epithelial cell layers the outermost thin cuticle, a densely packed keratinized cortex, and a central medulla of cuboidal cells. The hair follicle consists of four major components (1) internal root sheath (internal root sheath cuticle, granular layer, pale epithelial layer) (2) external root sheath (several layers similar to the epidermis) (3) dermal papilla (connective tissue) and (4) hair matrix (comparable to the stratum basale of the epidermis). 

The process of keratinization is continuous in the surface epidermis, while in the hair follicle the matrix cells undergo periods of quiescence during which no mitotic activity occurs. This cyclic activity of the hair bulb allows for the seasonal change in the hair coat of domestic animals. The length of time to regrow new hairs depends 

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In discussing skin structure, we limit ourselves to those features of the membrane which are pertinent to drag delivery in particular, to the stratum corneum (SC), the outermost layer wherein skin s barrier function principally resides. Macroscopically, skin comprises two main layers the epidermis and the dermis ( 0.1 and 1 mm in thickness, respectively) (see Figure 8.1). The dermal-epidermal junction is highly convoluted ensuring a maximal contact area. Other anatomical features of the skin of interest are the appendageal structures the hair follicles, nails and sweat glands. 

Additional keying information can come from certain other structural features which are present in a retron- or partial-retron-containing substructure. These ancillary keying elements can consist of functional groups, stereocenters, rings or appendages. Consider target structure 5... 

Algorithms for machine-generated syntheses by application of connective transforms to target structures containing appendages, medium-sized rings, etc. have been described. ... 

Appendage. A structural subunit consisting of one or more carbon atoms and their substituents which is bonded to a ring or functional group origin. 

The synthesis of ovalicin was accomplished following a line of analysis which was totally different from that employed for the synthesis of the structural relative fumagillol. The plan for ovalicin was based on S-goal, appendage, stereochemical and functional group derived strategies. A key requirement for the synthesis was the stereospecific construction of the -l,4-pentadienyl subunit, which was achieved by a method of potentially wide utility. 

Recently, a novel class of prostaglandin derivatives, PG-1,15-lactones (Fig. 1) of both E [16] and F [17] series, has been reported to occur in the opisthobranch mollusc Tethys fimbria, along with smaller amounts of some of the corresponding PGs. Some lactones were present mainly in the mucous secretion and dorsal appendages known as cerata, while others were more abundant in the mantle. Fatty acid esters of PGF-1,15-lactones (C9 and Cu) were found only in T. fimbria eggmasses and reproductive glands (ovotestis). The structural variety of the lactones and the data on their distribution in the body... 

Disconnection of that appendage-ring bond was a key step in the synthesis of ovalicin, a close structural relative to fumagillol.16... 

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