Abstract: Macrolides of the general structural Formula I: ##STR1## have been prepared. These macrolides are antagonists of FK-506-type immunosuppressants and are useful for modifying dosages of FK-506-type immunosuppressants in the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. Furthermore, the compounds of the present invention may have utility as antidotes for overdoses of FK-506-type immunosuppressants. In addition, these macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants.

Abstract: A process is described for the stereocontrolled synthesis of (3R,4R)-3-[(1R)-1-hydroxyethyl]-4-benzoyloxyazetidin-2-ones and their derivatives by cycloaddition involving an imine and a ketone, generated from 3(S)-hydroxybutyrate which are useful intermediates in the synthesis of carbapenem antibiotics.

Abstract: Novel C-3" and C-4" halogen-substituted macrolides of FK-506 type structural Formula I: ##STR1## are described. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases (such as juvenile-onset diabetes melitus, multiple sclerosis and rheumatoid arthritis), infectious diseases and/or the prevention of rejection of foreign organ transplants, e.g. bone marrow and heart transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses such as: psoriasis, atopical dermatitiis, contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis, Lichen planus, Pemphigus, bullous Pemphigoid, Epidermolysis bullosa, urticaria, angioedemas, vasulitides erythemas, cutaneous eosinophilias, Lupus erythematosus or Alopecia areata.

Abstract: 17.beta.-Acyl-4-aza-5.alpha.-androst-1-in-3-ones of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl R.sup.2 is methoxy, a monovalent radical selected from straight and branched chain alkyl of from 1-12 carbons, or monocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents, aralkyl selected from benzyl and phenethyl and heterocyclic selected from 2- or 4-pyridyl, 2-pyrrolyl, 2-furyl or thiophenyl; and R', R" and R'" are each selected from hydrogen and methyl and pharmaceutical formulations of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism, and benign prostatic hypertrophy.

Abstract: Described is a new L-679,934 (FK-506) antagonist, L-686,292, a C-15, C-31 bisdemethylated, derivative of L-683,590, produced under fermentation conditions utilizing the microorganism, Actinoplanacete sp. (Merck Culture Collection MA 6559) ATCC No. 53771. The macrolide reverses the immunosuppressant action of L-679,934 (FK-506), and can be used diagnostically as a tool to determine the presence of FK-506 macrolide type immunosuppressants in natural product broths, distinguishing such immunosuppressants from other chemical families such as the cycloporins.

Abstract: 17.beta.-Acyl-4-aza-5.alpha.-Androst-1-end-3-ones of the formula: ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.3 is cycloalkyl of from 4-8 carbons;and pharmaceutical formulation of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism, androgenic alopecia, prostatic carcinoma and benign prostatic hypertrophy.

Abstract: Described is a new process for producing the macrolide immunosuppressant, FK-506 under fermentation conditions utilizing the microorganism, Streptomyces sp., (Merck Culture Collection No. MA 6858) ATCC No. 55098. The immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Abstract: A process for dehydrogenating a compound of the formula ##STR1## which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce a .DELTA..sup.1 double bond.

Abstract: A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 .mu.g FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H.sub.2 N-Gly-Val-Gln-Val-Glu-Thr-Ile-Ser-Pro- Gly-Asp-Gly-Arg-Thr-Phe-Pro-Lys- Ar g-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Gly-Lys-Lys-Phe-As p (wherein X is undefined). The HCB protein is isolated from the cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g., Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyzes the cis-trans isomerization of proline-containing peptide bonds.

Abstract: A novel single-pot trialkylsilyl trifluoromethanesulfonate (R.sub.3 Si--OTf) mediated process produces derivatives of 4-aza 3-keto steroids at the .alpha.-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the .alpha.-methylene carbon, of .DELTA.-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-.alpha. reductase.

Abstract: A process is described for the synthesis of diastereomeric 2-methyl-4-hydroxy-5-protected-hydroxy-hept-6-en-prolinolamides, which are useful as intermediates in the synthesis of the C.sub.10 -C.sub.18 chain of the macrolide structure for the immunosuppressant FK-506. These compounds are also useful as intermediates for preparing lactone ultraviolet radiation absorbers.

Abstract: A process for dehydrogenating a compound of the formula ##STR1## which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce a .DELTA..sup.1 double bond.

Abstract: A combination of a carbapenem of the formula: ##STR1## where R is H or CH.sub.3 and R.sup.1 is ##STR2## with a renal dipeptidase inhibitor is disclosed.

Abstract: Ring-expanded macrolides related to FK-506 have immunosuppressive activity.

Abstract: Novel hydroxymacrolide derivatives of the general structural Formula I: ##STR1## have been prepared from (a) suitable precursor(s) by selective reduction of the ketone at C-2. These macrolide immunosuppressants are useful in a human host for the treatment of autoimmune diseases (such as juvenile-onset diabetes melitus, multiple sclerosis and rheumatoid arthritis), infectious diseases and/or the prevention of rejection of foreign organ transplants, e.g. bone marrow and heart transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses such as: psoriasis, atopical dermatitiis, contact dermatitis and further eczematous dermatitises, seborrhoeic dermatitis, Lichen planus, Pemphigus, bullous Pemphigoid, Epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eospinphilias, Lupus erythematosus or Alopecia areata.

Abstract: New phosphonic acid derivatives are described which display antibacterial activity.

Abstract: Ring-expanded, immunosuppressive macrolides, are produced by heating and rearranging FK-506 and related compounds.

Abstract: 17.beta.-Acyl-4-aza-5.alpha.-androst-1-ene-3-ones of the formula ##STR1## wherein R is selected from hydrogen, methyl and ethyl andR.sup.2 is monocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents;and R', R" and R'" are each selected from hydrogen and methyl and pharmaceutical formulation of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism, androgenic alopecia, prostatic carcinoma and benign prostatic hypertrophy.

Abstract: New peptide derivatives .beta.-chloro-L-(Z)-dehydroglutamic acid are described which display antibacterial activity.

Abstract: Described is a new diphosphonate intermediate useful in a new process for producing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP), a new antihypercalcemic agent. The process involves a 3-step sequence starting with 4-phthalimidobutanoyl chloride which can be practiced as a "one-pot" reaction sequence, without employing PCl.sub.3 or H.sub.3 PO.sub.3. The new intermediate has the structure: ##STR1## where n=1-5.